1-930163-G-T

Variant names:

• chr1-930163-G-T
• rs370992396
• NM_001385641.1:c.618G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001385641.1(SAMD11):​c.618G>T​(p.Gly206Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,678 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. Synonymous variant affecting the same amino acid position (i.e. G206G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SAMD11 NM_001385641.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 0 publications found

Genes affected

SAMD11 (HGNC:28706): (sterile alpha motif domain containing 11) Predicted to enable several functions, including histone binding activity; protein domain specific binding activity; and protein self-association. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SAMD11 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Franklin by Genoox

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.59 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385641.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD11	NM_001385641.1	MANE Select	c.618G>T	p.Gly206Gly	synonymous	Exon 3 of 14	NP_001372570.1	A0A087WU74
	SAMD11	NM_001385640.1		c.618G>T	p.Gly206Gly	synonymous	Exon 3 of 14	NP_001372569.1	A0A087WX24
	SAMD11	NM_152486.4		c.81G>T	p.Gly27Gly	synonymous	Exon 3 of 14	NP_689699.3	Q96NU1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD11	ENST00000616016.5	TSL:5 MANE Select	c.618G>T	p.Gly206Gly	synonymous	Exon 3 of 14	ENSP00000478421.2	A0A087WU74
	SAMD11	ENST00000968543.1		c.618G>T	p.Gly206Gly	synonymous	Exon 3 of 14	ENSP00000638602.1
	SAMD11	ENST00000618323.5	TSL:5	c.618G>T	p.Gly206Gly	synonymous	Exon 3 of 14	ENSP00000480678.2	A0A087WX24

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1403678 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 692976

African (AFR) AF: 0.00 AC: 0 AN: 32094

American (AMR) AF: 0.00 AC: 0 AN: 36184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25238

East Asian (EAS) AF: 0.00 AC: 0 AN: 36052

South Asian (SAS) AF: 0.00 AC: 0 AN: 79826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082068

Other (OTH) AF: 0.00 AC: 0 AN: 58176

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		-2.6
PromoterAI		-0.030	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs370992396; hg19: chr1-865543;