6-70858135-T-C

Position:

• chr6-70858135-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001044305.3(SMAP1):​c.1175T>C​(p.Val392Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SMAP1 NM_001044305.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49

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]

B3GAT2 (HGNC:922): (beta-1,3-glucuronyltransferase 2) The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes the transfer of a beta-1,3 linked glucuronic acid to a terminal galactose in different glycoproteins or glycolipids containing a Gal-beta-1-4GlcNAc or Gal-beta-1-3GlcNAc residue. The encoded protein is involved in the synthesis of the human natural killer-1 (HNK-1) carbohydrate epitope, a sulfated trisaccharide implicated in cellular migration and adhesion in the nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12847659).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAP1	NM_001044305.3	c.1175T>C	p.Val392Ala	missense_variant	10/11	ENST00000370455.8	NP_001037770.1
B3GAT2	NM_080742.3	c.*3528A>G		3_prime_UTR_variant	4/4	ENST00000230053.11	NP_542780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAP1	ENST00000370455.8	c.1175T>C	p.Val392Ala	missense_variant	10/11	1	NM_001044305.3	ENSP00000359484	P3
B3GAT2	ENST00000230053.11	c.*3528A>G		3_prime_UTR_variant	4/4	1	NM_080742.3	ENSP00000230053	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2022

The c.1175T>C (p.V392A) alteration is located in exon 10 (coding exon 10) of the SMAP1 gene. This alteration results from a T to C substitution at nucleotide position 1175, causing the valine (V) at amino acid position 392 to be replaced by an alanine (A). 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	0.078
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	.;.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.022
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;.;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N;N;.
REVEL	Benign	0.058
Sift	Benign	0.040	D;D;D;.
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.0010	B;B;B;.
Vest4		0.17
MutPred		0.22		.;.;Loss of catalytic residue at V392 (P = 0.1088);.;
MVP		0.21
MPC		0.15
ClinPred		0.69	D
GERP RS		4.4
Varity_R		0.044
gMVP		0.25

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.

Other links and lift over

hg19: chr6-71567838;