dbSNP rs1770617952: SMAP1:p.Asp217Glu (chr6-70837015-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001044305.3(SMAP1):c.651T>A(p.Asp217Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,593,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2676967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3 link	c.651T>A	p.Asp217Glu	missense_variant	Exon 7 of 11	ENST00000370455.8	NP_001037770.1	Q8IYB5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAP1	ENST00000370455.8 link	c.651T>A	p.Asp217Glu	missense_variant	Exon 7 of 11	1	NM_001044305.3	ENSP00000359484.3		Q8IYB5-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32282

American (AMR)

AF:

0.00

AC:

AN:

42804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25722

East Asian (EAS)

AF:

0.00

AC:

AN:

38578

South Asian (SAS)

AF:

0.00

AC:

AN:

81390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103146

Other (OTH)

AF:

0.0000168

AC:

AN:

59428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.000131

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.651T>A (p.D217E) alteration is located in exon 7 (coding exon 7) of the SMAP1 gene. This alteration results from a T to A substitution at nucleotide position 651, causing the aspartic acid (D) at amino acid position 217 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

.;.;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.8

.;.;M;.

PhyloP100

2.2

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.0

D;D;D;.

REVEL

Benign

0.11

Sift

Uncertain

0.0010

D;D;D;.

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.93

P;D;D;.

Vest4

0.41

MutPred

0.16

.;.;Loss of phosphorylation at T215 (P = 0.2552);.;

MVP

0.50

MPC

0.54

ClinPred

0.98

GERP RS

1.3

Varity_R

0.23

gMVP

0.19

Mutation Taster

=92/8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over