NM_001304366.2:c.650C>G

Variant names:

• chr3-169926912-C-G
• NM_001304366.2:c.650C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304366.2(SAMD7):​c.650C>G​(p.Pro217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. P217L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SAMD7 NM_001304366.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

Genes affected

SAMD7 (HGNC:25394): (sterile alpha motif domain containing 7) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19370872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD7	NM_001304366.2	c.650C>G	p.Pro217Arg	missense_variant	Exon 6 of 9	ENST00000335556.7	NP_001291295.1
SAMD7	NM_182610.4	c.650C>G	p.Pro217Arg	missense_variant	Exon 6 of 9		NP_872416.1
SAMD7	NR_130713.2	n.1129C>G		non_coding_transcript_exon_variant	Exon 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD7	ENST00000335556.7	c.650C>G	p.Pro217Arg	missense_variant	Exon 6 of 9	1	NM_001304366.2	ENSP00000334668.3
SAMD7	ENST00000428432.6	c.650C>G	p.Pro217Arg	missense_variant	Exon 6 of 9	1		ENSP00000391299.2
SAMD7	ENST00000487910.1	n.*466C>G		non_coding_transcript_exon_variant	Exon 6 of 9	1		ENSP00000420460.1
SAMD7	ENST00000487910.1	n.*466C>G		3_prime_UTR_variant	Exon 6 of 9	1		ENSP00000420460.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0068	T;T
Eigen	Benign	-0.013
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.088
Sift	Benign	0.031	D;D
Sift4G	Benign	0.20	T;T
Polyphen		0.97	D;D
Vest4		0.28
MutPred		0.16		Loss of phosphorylation at Y218 (P = 0.1009);Loss of phosphorylation at Y218 (P = 0.1009);
MVP		0.51
MPC		0.52
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.092
gMVP		0.065

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-169644700;