rs408067

Variant names:

• chr17-2303942-C-G
• rs408067
• ENST00000572709.5:c.-5+465C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000572709.5(SRR):​c.-5+465C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 298,110 control chromosomes in the GnomAD database, including 44,037 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (23449 hom., cov: 32)
  • Exomes 𝑓: 0.50 (20588 hom.)
• Consequence: SRR ENST00000572709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 14 publications found

Genes affected

SRR (HGNC:14398): (serine racemase) Enables several functions, including L-serine ammonia-lyase activity; PDZ domain binding activity; and anion binding activity. Involved in pyruvate biosynthetic process; response to lipopolysaccharide; and serine family amino acid metabolic process. Located in cytoplasm and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

SMG6 (HGNC:17809): (SMG6 nonsense mediated mRNA decay factor) This gene encodes a component of the telomerase ribonucleoprotein complex responsible for the replication and maintenance of chromosome ends. The encoded protein also plays a role in the nonsense-mediated mRNA decay (NMD) pathway, providing the endonuclease activity near the premature translation termination codon that is needed to initiate NMD. Alternatively spliced transcript variants encoding distinct protein isoforms have been described. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG6	NM_017575.5	c.-222G>C		upstream_gene_variant		ENST00000263073.11	NP_060045.4
SRR	NM_021947.3	c.-80C>G		upstream_gene_variant		ENST00000344595.10	NP_068766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.-222G>C		upstream_gene_variant		1	NM_017575.5	ENSP00000263073.5
SRR	ENST00000344595.10	c.-80C>G		upstream_gene_variant		1	NM_021947.3	ENSP00000339435.5

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82193 AN: 151606 Hom.: 23438 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.558

GnomAD4 exome AF: 0.498 AC: 72926 AN: 146396 Hom.: 20588 Cov.: 2 AF XY: 0.502 AC XY: 39970 AN XY: 79672

African (AFR) AF: 0.184 AC: 662 AN: 3592

American (AMR) AF: 0.389 AC: 864 AN: 2220

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 2137 AN: 4040

East Asian (EAS) AF: 0.577 AC: 3523 AN: 6106

South Asian (SAS) AF: 0.556 AC: 9960 AN: 17920

European-Finnish (FIN) AF: 0.474 AC: 5440 AN: 11480

Middle Eastern (MID) AF: 0.425 AC: 296 AN: 696

European-Non Finnish (NFE) AF: 0.502 AC: 46142 AN: 91876

Other (OTH) AF: 0.461 AC: 3902 AN: 8466

GnomAD4 genome AF: 0.542 AC: 82236 AN: 151714 Hom.: 23449 Cov.: 32 AF XY: 0.545 AC XY: 40420 AN XY: 74146

African (AFR) AF: 0.359 AC: 14856 AN: 41422

American (AMR) AF: 0.596 AC: 9086 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2266 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3510 AN: 5078

South Asian (SAS) AF: 0.546 AC: 2633 AN: 4822

European-Finnish (FIN) AF: 0.614 AC: 6443 AN: 10490

Middle Eastern (MID) AF: 0.548 AC: 159 AN: 290

European-Non Finnish (NFE) AF: 0.612 AC: 41546 AN: 67874

Other (OTH) AF: 0.558 AC: 1173 AN: 2104

Alfa AF: 0.571 Hom.: 3099

Bravo AF: 0.534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.9
DANN	Benign	0.87
PhyloP100		-0.47
PromoterAI		-0.11	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs408067; hg19: chr17-2207236;