Genetic Variant NM_001044305.3:c.424T>C (chr6-70791698-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001044305.3(SMAP1):c.424T>C(p.Ser142Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,612,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 1 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0314807).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3 link	c.424T>C	p.Ser142Pro	missense_variant	Exon 5 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.424T>C	p.Ser142Pro	missense_variant	Exon 5 of 11	1	NM_001044305.3	ENSP00000359484.3		Q8IYB5-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00115

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:

0.000105

AC:

AN:

248530

AF XY:

0.0000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00139

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1460680

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.000505

AC:

AN:

39612

South Asian (SAS)

AF:

0.00

AC:

AN:

86122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111508

Other (OTH)

AF:

0.0000994

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000993

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 29, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.424T>C (p.S142P) alteration is located in exon 5 (coding exon 5) of the SMAP1 gene. This alteration results from a T to C substitution at nucleotide position 424, causing the serine (S) at amino acid position 142 to be replaced by a proline (P). 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

0.099

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

T;.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

PhyloP100

5.8

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.82

N;.;D

REVEL

Benign

0.18

Sift

Uncertain

0.017

D;.;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.35

MVP

0.36

MPC

0.17

ClinPred

0.13

GERP RS

5.5

Varity_R

0.29

gMVP

0.39

Mutation Taster

=70/30

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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NM_001044305.3:c.424T>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