rs408067

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.461

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

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.558

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

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: rs408067; hg19: chr17-2207236;