1-926010-G-A

Variant names:

• chr1-926010-G-A
• rs889842126
• NM_001385641.1:c.606G>A

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.606G>A​(p.Pro202Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,030 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. P202P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SAMD11 NM_001385641.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• 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=-0.63).
• BP7: Synonymous conserved (PhyloP=-1 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.606G>A	p.Pro202Pro	synonymous	Exon 2 of 14	NP_001372570.1	A0A087WU74
	SAMD11	NM_001385640.1		c.606G>A	p.Pro202Pro	synonymous	Exon 2 of 14	NP_001372569.1	A0A087WX24
	SAMD11	NM_152486.4		c.69G>A	p.Pro23Pro	synonymous	Exon 2 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.606G>A	p.Pro202Pro	synonymous	Exon 2 of 14	ENSP00000478421.2	A0A087WU74
	SAMD11	ENST00000968543.1		c.606G>A	p.Pro202Pro	synonymous	Exon 2 of 14	ENSP00000638602.1
	SAMD11	ENST00000618323.5	TSL:5	c.606G>A	p.Pro202Pro	synonymous	Exon 2 of 14	ENSP00000480678.2	A0A087WX24

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459030 Hom.: 0 Cov.: 30 AF XY: 0.00000827 AC XY: 6 AN XY: 725898

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111856

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.8
DANN	Benign	0.92
PhyloP100		-1.0
PromoterAI		0.015	Neutral
Mutation Taster		=100/0	polymorphism

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: rs889842126; hg19: chr1-861390; COSMIC: COSV105208975; COSMIC: COSV105208975;