chr17-2304032-G-A

Variant names:

• chr17-2304032-G-A
• rs3744270
• NM_021947.3:c.-5+15G>A

Variant summary

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

The NM_021947.3(SRR):​c.-5+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 245,490 control chromosomes in the GnomAD database, including 12,277 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 0.25 (6342 hom., cov: 30)
  • Exomes 𝑓: 0.34 (5935 hom.)
• Consequence: SRR NM_021947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 23 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRR	NM_021947.3	c.-5+15G>A		intron_variant	Intron 1 of 7	ENST00000344595.10	NP_068766.1
SMG6	NM_017575.5	c.-312C>T		upstream_gene_variant		ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRR	ENST00000344595.10	c.-5+15G>A		intron_variant	Intron 1 of 7	1	NM_021947.3	ENSP00000339435.5
SMG6	ENST00000263073.11	c.-312C>T		upstream_gene_variant		1	NM_017575.5	ENSP00000263073.5

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38584 AN: 151782 Hom.: 6342 Cov.: 30

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.344 AC: 32162 AN: 93596 Hom.: 5935 Cov.: 0 AF XY: 0.344 AC XY: 16442 AN XY: 47826

African (AFR) AF: 0.0712 AC: 176 AN: 2472

American (AMR) AF: 0.418 AC: 900 AN: 2154

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1502 AN: 3388

East Asian (EAS) AF: 0.125 AC: 831 AN: 6634

South Asian (SAS) AF: 0.244 AC: 718 AN: 2942

European-Finnish (FIN) AF: 0.372 AC: 2694 AN: 7242

Middle Eastern (MID) AF: 0.348 AC: 176 AN: 506

European-Non Finnish (NFE) AF: 0.372 AC: 23028 AN: 61900

Other (OTH) AF: 0.336 AC: 2137 AN: 6358

GnomAD4 genome AF: 0.254 AC: 38581 AN: 151894 Hom.: 6342 Cov.: 30 AF XY: 0.253 AC XY: 18758 AN XY: 74232

African (AFR) AF: 0.0617 AC: 2563 AN: 41512

American (AMR) AF: 0.355 AC: 5425 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3472

East Asian (EAS) AF: 0.0968 AC: 496 AN: 5124

South Asian (SAS) AF: 0.163 AC: 784 AN: 4824

European-Finnish (FIN) AF: 0.341 AC: 3598 AN: 10546

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23309 AN: 67836

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.290 Hom.: 910

Bravo AF: 0.250

Asia WGS AF: 0.120 AC: 418 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.77
DANN	Benign	0.85
PhyloP100		-2.9
PromoterAI		-0.048	Neutral
Mutation Taster		=100/0	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: rs3744270; hg19: chr17-2207326;