6-70856922-T-C

Variant names:

• chr6-70856922-T-C
• rs1771449070
• NM_001044305.3:c.853T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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: 7.19
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001044305.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAP1	NM_001044305.3	MANE Select	c.853T>C	p.Phe285Leu	missense	Exon 9 of 11	NP_001037770.1	Q8IYB5-1
	B3GAT2	NM_080742.3	MANE Select	c.*4741A>G		3_prime_UTR	Exon 4 of 4	NP_542780.1	Q9NPZ5
	SMAP1	NM_001281440.1		c.823T>C	p.Phe275Leu	missense	Exon 9 of 11	NP_001268369.1	A0A087X1X9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAP1	ENST00000370455.8	TSL:1 MANE Select	c.853T>C	p.Phe285Leu	missense	Exon 9 of 11	ENSP00000359484.3	Q8IYB5-1
	SMAP1	ENST00000619054.4	TSL:1	c.823T>C	p.Phe275Leu	missense	Exon 9 of 11	ENSP00000484538.1	A0A087X1X9
	SMAP1	ENST00000316999.9	TSL:1	c.772T>C	p.Phe258Leu	missense	Exon 8 of 10	ENSP00000313382.5	Q8IYB5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	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
Mutation Taster		=31/69	disease causing

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

Other links and lift over

dbSNP: rs1771449070; hg19: chr6-71566625;