NM_001044305.3:c.363T>A

Variant names:

• chr6-70773374-T-A
• rs147135200
• NM_001044305.3:c.363T>A

Variant summary

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

The NM_001044305.3(SMAP1):​c.363T>A​(p.Asp121Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SMAP1 NM_001044305.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• 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=0.35684258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3	c.363T>A	p.Asp121Glu	missense_variant	Exon 4 of 11	ENST00000370455.8	NP_001037770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAP1	ENST00000370455.8	c.363T>A	p.Asp121Glu	missense_variant	Exon 4 of 11	1	NM_001044305.3	ENSP00000359484.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422866 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 707666

African (AFR) AF: 0.00 AC: 0 AN: 32718

American (AMR) AF: 0.00 AC: 0 AN: 42454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25322

East Asian (EAS) AF: 0.00 AC: 0 AN: 39232

South Asian (SAS) AF: 0.00 AC: 0 AN: 82614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083814

Other (OTH) AF: 0.0000170 AC: 1 AN: 58900

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	.;.;T;.;T
Eigen	Benign	0.084
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D;D;D;D;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N;N;N;.;.
PhyloP100		1.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.4	N;N;N;.;D
REVEL	Benign	0.26
Sift	Benign	0.38	T;T;T;.;D
Sift4G	Benign	0.56	T;T;T;T;D
Polyphen		0.99	D;D;D;.;.
Vest4		0.69
MutPred		0.49		Gain of ubiquitination at K122 (P = 0.1191);Gain of ubiquitination at K122 (P = 0.1191);Gain of ubiquitination at K122 (P = 0.1191);.;.;
MVP		0.61
MPC		0.45
ClinPred		0.89	D
GERP RS		0.63
PromoterAI		0.018	Neutral
Varity_R		0.17
gMVP		0.30
Mutation Taster		=41/59	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: rs147135200; hg19: chr6-71483077;