6-70856922-T-C

Position:

• chr6-70856922-T-C

Variant summary

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

The NM_001044305.3(SMAP1):​c.853T>C​(p.Phe285Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMAP1 NM_001044305.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAP1	NM_001044305.3	c.853T>C	p.Phe285Leu	missense_variant	9/11	ENST00000370455.8	NP_001037770.1
B3GAT2	NM_080742.3	c.*4741A>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.853T>C	p.Phe285Leu	missense_variant	9/11	1	NM_001044305.3	ENSP00000359484.3
B3GAT2	ENST00000230053.11	c.*4741A>G		3_prime_UTR_variant	4/4	1	NM_080742.3	ENSP00000230053.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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 28, 2024

The c.853T>C (p.F285L) alteration is located in exon 9 (coding exon 9) of the SMAP1 gene. This alteration results from a T to C substitution at nucleotide position 853, causing the phenylalanine (F) at amino acid position 285 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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	.;.;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.8	.;.;M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.3	D;D;D;.
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.74
MutPred		0.44		.;.;Gain of glycosylation at T289 (P = 0.1412);.;
MVP		0.34
MPC		0.54
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.63
gMVP		0.52

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

Other links and lift over

dbSNP: rs1771449070; hg19: chr6-71566625;