6-70860242-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001044305.3(SMAP1):c.1312C>A(p.Pro438Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000837 in 1,613,418 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 1 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

Publications

1 publications found

Variant links:

Genes affected

SMAP1 (HGNC:19651): (small ArfGAP 1) The protein encoded by this gene is similar to the mouse stromal membrane-associated protein-1. This similarity suggests that this human gene product is also a type II membrane glycoprotein involved in the erythropoietic stimulatory activity of stromal cells. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

SMAP1 links:

B3GAT2 (HGNC:922): (beta-1,3-glucuronyltransferase 2) The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes the transfer of a beta-1,3 linked glucuronic acid to a terminal galactose in different glycoproteins or glycolipids containing a Gal-beta-1-4GlcNAc or Gal-beta-1-3GlcNAc residue. The encoded protein is involved in the synthesis of the human natural killer-1 (HNK-1) carbohydrate epitope, a sulfated trisaccharide implicated in cellular migration and adhesion in the nervous system. [provided by RefSeq, Jul 2008]

B3GAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015593231).

BS2

High AC in GnomAd4 at 26 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001044305.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMAP1	NM_001044305.3	MANE Select	c.1312C>A	p.Pro438Thr	missense	Exon 11 of 11	NP_001037770.1	Q8IYB5-1
B3GAT2	NM_080742.3	MANE Select	c.*1421G>T		3_prime_UTR	Exon 4 of 4	NP_542780.1	Q9NPZ5
SMAP1	NM_001281440.1		c.1282C>A	p.Pro428Thr	missense	Exon 11 of 11	NP_001268369.1	A0A087X1X9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMAP1	ENST00000370455.8	TSL:1 MANE Select	c.1312C>A	p.Pro438Thr	missense	Exon 11 of 11	ENSP00000359484.3	Q8IYB5-1
SMAP1	ENST00000619054.4	TSL:1	c.1282C>A	p.Pro428Thr	missense	Exon 11 of 11	ENSP00000484538.1	A0A087X1X9
SMAP1	ENST00000316999.9	TSL:1	c.1231C>A	p.Pro411Thr	missense	Exon 10 of 10	ENSP00000313382.5	Q8IYB5-2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000879

AC:

AN:

250404

AF XY:

0.0000961

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.0000746

AC:

109

AN:

1461236

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33458

American (AMR)

AF:

0.000673

AC:

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000585

AC:

AN:

1111734

Other (OTH)

AF:

0.000166

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41532

American (AMR)

AF:

0.00124

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000767

Hom.:

Bravo

AF:

0.000249

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.6

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.015

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.69

M_CAP

Benign

0.0086

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

PhyloP100

1.8

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.58

REVEL

Benign

0.040

Sift

Benign

0.20

Sift4G

Benign

0.24

Polyphen

0.034

Vest4

0.065

MVP

0.26

MPC

0.14

ClinPred

0.031

GERP RS

0.60

Varity_R

0.029

gMVP

0.17

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over