Genetic Variant SMAP1:p.Asn101Ser (chr6-70755029-A-G) – 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.302A>G(p.Asn101Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000478 in 1,610,800 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.98

Publications

3 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=0.3585613).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3 link	c.302A>G	p.Asn101Ser	missense_variant	Exon 3 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.302A>G	p.Asn101Ser	missense_variant	Exon 3 of 11	1	NM_001044305.3	ENSP00000359484.3	Q8IYB5-1
SMAP1	ENST00000619054.4 link	c.272A>G	p.Asn91Ser	missense_variant	Exon 3 of 11	1		ENSP00000484538.1	A0A087X1X9
SMAP1	ENST00000316999.9 link	c.302A>G	p.Asn101Ser	missense_variant	Exon 3 of 10	1		ENSP00000313382.5	Q8IYB5-2
SMAP1	ENST00000370452.7 link	c.302A>G	p.Asn101Ser	missense_variant	Exon 3 of 11	2		ENSP00000359481.3	Q8IYB5-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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

GnomAD2 exomes

AF:

0.0000678

AC:

AN:

250668

AF XY:

0.0000664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000494

AC:

AN:

1458722

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

725684

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33362

American (AMR)

AF:

0.000157

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39528

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86052

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000487

AC:

AN:

1109798

Other (OTH)

AF:

0.0000332

AC:

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41452

American (AMR)

AF:

0.000131

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67940

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000405

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 03, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.302A>G (p.N101S) alteration is located in exon 3 (coding exon 3) of the SMAP1 gene. This alteration results from a A to G substitution at nucleotide position 302, causing the asparagine (N) at amino acid position 101 to be replaced by a serine (S). 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

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;.;T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.0097

MetaRNN

Benign

0.36

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L;.

PhyloP100

7.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.3

D;D;D;.

REVEL

Benign

0.20

Sift

Benign

0.20

T;T;T;.

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.88

P;P;B;.

Vest4

0.49

MutPred

0.57

Gain of phosphorylation at N101 (P = 0.0698);Gain of phosphorylation at N101 (P = 0.0698);Gain of phosphorylation at N101 (P = 0.0698);.;

MVP

0.47

MPC

0.44

ClinPred

0.14

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.22

gMVP

0.72

Mutation Taster

=76/24

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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6-70755029-A-G

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