Genetic Variant SMAP1:p.Ala212Val (chr6-70836999-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001044305.3(SMAP1):c.635C>T(p.Ala212Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,598,686 control chromosomes in the GnomAD database, including 16,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 3326 hom., cov: 32)

Exomes 𝑓: 0.10 ( 13257 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.446

Publications

23 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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.086791E-5).

BP6

Variant 6-70836999-C-T is Benign according to our data. Variant chr6-70836999-C-T is described in ClinVar as [Benign]. Clinvar id is 1297961.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3 link	c.635C>T	p.Ala212Val	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.635C>T	p.Ala212Val	missense_variant	Exon 7 of 11	1	NM_001044305.3	ENSP00000359484.3		Q8IYB5-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25344

AN:

151948

Hom.:

3324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.0652

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.0904

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0748

Gnomad OTH

AF:

0.146

GnomAD2 exomes

AF:

0.154

AC:

36914

AN:

239392

AF XY:

0.146

show subpopulations

Gnomad AFR exome

AF:

0.292

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.0679

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.0859

Gnomad NFE exome

AF:

0.0767

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.103

AC:

148522

AN:

1446620

Hom.:

13257

Cov.:

AF XY:

0.103

AC XY:

74032

AN XY:

718850

show subpopulations

African (AFR)

AF:

0.299

AC:

9766

AN:

32684

American (AMR)

AF:

0.204

AC:

8846

AN:

43362

Ashkenazi Jewish (ASJ)

AF:

0.0683

AC:

1766

AN:

25862

East Asian (EAS)

AF:

0.533

AC:

20636

AN:

38740

South Asian (SAS)

AF:

0.153

AC:

12607

AN:

82592

European-Finnish (FIN)

AF:

0.0861

AC:

4546

AN:

52782

Middle Eastern (MID)

AF:

0.107

AC:

609

AN:

5684

European-Non Finnish (NFE)

AF:

0.0745

AC:

82371

AN:

1105238

Other (OTH)

AF:

0.124

AC:

7375

AN:

59676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

5530

11060

16591

22121

27651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.167

AC:

25380

AN:

152066

Hom.:

3326

Cov.:

AF XY:

0.169

AC XY:

12589

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.300

AC:

12425

AN:

41444

American (AMR)

AF:

0.162

AC:

2482

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0652

AC:

226

AN:

3466

East Asian (EAS)

AF:

0.566

AC:

2931

AN:

5176

South Asian (SAS)

AF:

0.176

AC:

848

AN:

4824

European-Finnish (FIN)

AF:

0.0904

AC:

956

AN:

10574

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0748

AC:

5087

AN:

67988

Other (OTH)

AF:

0.152

AC:

321

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

976

1951

2927

3902

4878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.108

Hom.:

4414

Bravo

AF:

0.182

TwinsUK

AF:

0.0693

AC:

257

ALSPAC

AF:

0.0786

AC:

303

ESP6500AA

AF:

0.291

AC:

1280

ESP6500EA

AF:

0.0751

AC:

646

ExAC

AF:

0.155

AC:

18829

Asia WGS

AF:

0.344

AC:

1193

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 24, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.022

.;.;T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.77

T;T;T;T

MetaRNN

Benign

0.000091

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

.;.;L;.

PhyloP100

0.45

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N;N;.

REVEL

Benign

0.038

Sift

Benign

0.20

T;T;T;.

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.66

P;B;B;.

Vest4

0.049

MPC

0.12

ClinPred

0.0091

GERP RS

3.4

Varity_R

0.038

gMVP

0.19

Mutation Taster

=97/3

polymorphism (auto)

(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.

6-70836999-C-T

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