NM_001044305.3:c.80A>T

Variant names:

• chr6-70668103-A-T
• rs767731066
• NM_001044305.3:c.80A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001044305.3(SMAP1):​c.80A>T​(p.Glu27Val) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E27A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMAP1 NM_001044305.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45
• 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3	c.80A>T	p.Glu27Val	missense_variant	Exon 1 of 11	ENST00000370455.8	NP_001037770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAP1	ENST00000370455.8	c.80A>T	p.Glu27Val	missense_variant	Exon 1 of 11	1	NM_001044305.3	ENSP00000359484.3
SMAP1	ENST00000316999.9	c.80A>T	p.Glu27Val	missense_variant	Exon 1 of 10	1		ENSP00000313382.5
SMAP1	ENST00000370452.7	c.80A>T	p.Glu27Val	missense_variant	Exon 1 of 11	2		ENSP00000359481.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;.;T
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.0099
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L
PhyloP100		5.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.067	B;B;D
Vest4		0.71
MutPred		0.51		Loss of disorder (P = 0.0191);Loss of disorder (P = 0.0191);Loss of disorder (P = 0.0191);
MVP		0.48
MPC		2.4
ClinPred		0.99	D
GERP RS		2.2
PromoterAI		-0.0045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.78
Mutation Taster		=37/63	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: rs767731066; hg19: chr6-71377806;