Genetic Variant SMAP1:p.Glu27Ala (chr6-70668103-A-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001044305.3(SMAP1):c.80A>C(p.Glu27Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000125 in 1,603,642 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: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27891418).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3 link	c.80A>C	p.Glu27Ala	missense_variant	Exon 1 of 11	ENST00000370455.8	NP_001037770.1	Q8IYB5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMAP1	ENST00000370455.8 link	c.80A>C	p.Glu27Ala	missense_variant	Exon 1 of 11	1	NM_001044305.3	ENSP00000359484.3	Q8IYB5-1
SMAP1	ENST00000316999.9 link	c.80A>C	p.Glu27Ala	missense_variant	Exon 1 of 10	1		ENSP00000313382.5	Q8IYB5-2
SMAP1	ENST00000370452.7 link	c.80A>C	p.Glu27Ala	missense_variant	Exon 1 of 11	2		ENSP00000359481.3	Q8IYB5-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000251

AC:

AN:

239200

AF XY:

0.0000154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000458

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1451484

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

722060

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31660

American (AMR)

AF:

0.0000227

AC:

AN:

43990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25774

East Asian (EAS)

AF:

0.00

AC:

AN:

38502

South Asian (SAS)

AF:

0.00

AC:

AN:

84896

European-Finnish (FIN)

AF:

0.0000376

AC:

AN:

53136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1107852

Other (OTH)

AF:

0.00

AC:

AN:

59968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 18, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.80A>C (p.E27A) alteration is located in exon 1 (coding exon 1) of the SMAP1 gene. This alteration results from a A to C substitution at nucleotide position 80, causing the glutamic acid (E) at amino acid position 27 to be replaced by an alanine (A). 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

0.61

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;.;T

Eigen

Benign

-0.0071

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

T;T;D

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

L;L;L

PhyloP100

5.4

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.018

D;D;D

Sift4G

Uncertain

0.028

D;D;D

Polyphen

0.10

B;B;D

Vest4

0.62

MutPred

0.42

Loss of methylation at K31 (P = 0.035);Loss of methylation at K31 (P = 0.035);Loss of methylation at K31 (P = 0.035);

MVP

0.48

MPC

2.3

ClinPred

0.90

GERP RS

2.2

PromoterAI

-0.0039

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.62

gMVP

0.76

Mutation Taster

=35/65

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

chr6-70668103-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over