Variant 6-70798712-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001044305.3(SMAP1):c.551C>T(p.Pro184Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,558,584 control chromosomes in the GnomAD database, including 6 homozygotes. 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: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005534649).

BS2

High AC in GnomAd4 at 205 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAP1	NM_001044305.3 linkuse as main transcript	c.551C>T	p.Pro184Leu	missense_variant	6/11	ENST00000370455.8	NP_001037770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAP1	ENST00000370455.8 linkuse as main transcript	c.551C>T	p.Pro184Leu	missense_variant	6/11	1	NM_001044305.3	ENSP00000359484	P3	Q8IYB5-1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

151340

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000970

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.000966

GnomAD3 exomes

AF:

0.00113

AC:

226

AN:

200204

Hom.:

AF XY:

0.00126

AC XY:

136

AN XY:

108198

show subpopulations

Gnomad AFR exome

AF:

0.0000764

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000417

Gnomad SAS exome

AF:

0.0000424

Gnomad FIN exome

AF:

0.000669

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.00158

GnomAD4 exome

AF:

0.00188

AC:

2644

AN:

1407138

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

1281

AN XY:

697406

show subpopulations

Gnomad4 AFR exome

AF:

0.000356

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.0000402

Gnomad4 EAS exome

AF:

0.000106

Gnomad4 SAS exome

AF:

0.0000661

Gnomad4 FIN exome

AF:

0.000829

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

151446

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

73988

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00171

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.000970

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00135

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00117

AC:

ExAC

AF:

0.000929

AC:

112

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

Apr 01, 2024

The c.551C>T (p.P184L) alteration is located in exon 6 (coding exon 6) of the SMAP1 gene. This alteration results from a C to T substitution at nucleotide position 551, causing the proline (P) at amino acid position 184 to be replaced by a leucine (L). 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

0.060

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.027

.;.;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.0021

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.58

T;T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.0055

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.0

D;D;D;.

REVEL

Benign

0.028

Sift

Uncertain

0.021

D;D;T;.

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.0030

B;B;B;.

Vest4

0.18

MVP

0.14

MPC

0.13

ClinPred

0.019

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over