7-93101351-C-T

Position:

• chr7-93101351-C-T

Variant summary

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

The NM_017654.4(SAMD9):​c.4747G>A​(p.Ala1583Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,542 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: SAMD9 NM_017654.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.21

Genes affected

SAMD9 (HGNC:1348): (sterile alpha motif domain containing 9) This gene encodes a sterile alpha motif domain-containing protein. The encoded protein localizes to the cytoplasm and may play a role in regulating cell proliferation and apoptosis. Mutations in this gene are the cause of normophosphatemic familial tumoral calcinosis. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD9	NM_017654.4	c.4747G>A	p.Ala1583Thr	missense_variant	3/3	ENST00000379958.3	NP_060124.2
SAMD9	NM_001193307.2	c.4747G>A	p.Ala1583Thr	missense_variant	2/2		NP_001180236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD9	ENST00000379958.3	c.4747G>A	p.Ala1583Thr	missense_variant	3/3	1	NM_017654.4	ENSP00000369292	P1
SAMD9	ENST00000620985.4	c.4747G>A	p.Ala1583Thr	missense_variant	2/2	2		ENSP00000484636	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 250814 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135626

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460542 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 726612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;.
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.2	.;D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.47
MutPred		0.41		Gain of disorder (P = 0.1374);Gain of disorder (P = 0.1374);
MVP		0.69
MPC		0.65
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.66
gMVP		0.90

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: rs779813128; hg19: chr7-92730664;