Variant chr6-70773414-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001044305.3(SMAP1):c.403G>A(p.Ala135Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000428 in 1,400,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1334624).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAP1	NM_001044305.3 linkuse as main transcript	c.403G>A	p.Ala135Thr	missense_variant	4/11	ENST00000370455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAP1	ENST00000370455.8 linkuse as main transcript	c.403G>A	p.Ala135Thr	missense_variant	4/11	1	NM_001044305.3	P3	Q8IYB5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000428

AC:

AN:

1400422

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

696792

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000562

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.403G>A (p.A135T) alteration is located in exon 4 (coding exon 4) of the SMAP1 gene. This alteration results from a G to A substitution at nucleotide position 403, causing the alanine (A) at amino acid position 135 to be replaced by a threonine (T). 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

0.068

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.019

.;.;T;.;T

Eigen

Benign

0.081

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.72

T;T;T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;.;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

N;N;N;.;N

REVEL

Benign

0.039

Sift

Benign

0.58

T;T;T;.;T

Sift4G

Benign

0.58

T;T;T;T;T

Polyphen

0.0010

B;B;B;.;.

Vest4

0.14

MutPred

0.39

Gain of glycosylation at A135 (P = 0.0551);Gain of glycosylation at A135 (P = 0.0551);Gain of glycosylation at A135 (P = 0.0551);.;.;

MVP

0.18

MPC

0.12

ClinPred

0.68

GERP RS

4.6

Varity_R

0.040

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over