chr6-70852657-C-T

Variant names:

• chr6-70852657-C-T
• NM_001044305.3:c.782C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001044305.3(SMAP1):​c.782C>T​(p.Pro261Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 4.18
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27057606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3	c.782C>T	p.Pro261Leu	missense_variant	Exon 8 of 11	ENST00000370455.8	NP_001037770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAP1	ENST00000370455.8	c.782C>T	p.Pro261Leu	missense_variant	Exon 8 of 11	1	NM_001044305.3	ENSP00000359484.3
SMAP1	ENST00000619054.4	c.752C>T	p.Pro251Leu	missense_variant	Exon 8 of 11	1		ENSP00000484538.1
SMAP1	ENST00000316999.9	c.701C>T	p.Pro234Leu	missense_variant	Exon 7 of 10	1		ENSP00000313382.5
SMAP1	ENST00000370452.7	c.701C>T	p.Pro234Leu	missense_variant	Exon 7 of 11	2		ENSP00000359481.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 30, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.782C>T (p.P261L) alteration is located in exon 8 (coding exon 8) of the SMAP1 gene. This alteration results from a C to T substitution at nucleotide position 782, causing the proline (P) at amino acid position 261 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	0.074
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	.;.;T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;.;M;.
PhyloP100		4.2
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.7	D;D;D;.
REVEL	Benign	0.064
Sift	Benign	0.041	D;D;D;.
Sift4G	Uncertain	0.059	T;T;T;T
Polyphen		0.65	P;P;P;.
Vest4		0.55
MutPred		0.40		.;.;Gain of stability (P = 0.0121);.;
MVP		0.18
MPC		0.15
ClinPred		0.97	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.070
gMVP		0.21
Mutation Taster		=89/11	polymorphism

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

hg19: chr6-71562360;