rs4523957

Variant names:

• chr17-2305605-G-T
• rs4523957
• NM_021947.3:c.-5+1588G>T

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+1588G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,094 control chromosomes in the GnomAD database, including 24,219 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 0.55 (24219 hom., cov: 32)
• Consequence: SRR NM_021947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 92 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRR	NM_021947.3	c.-5+1588G>T		intron_variant	Intron 1 of 7	ENST00000344595.10	NP_068766.1
SRR	NM_001304803.1	c.-280+1588G>T		intron_variant	Intron 1 of 6		NP_001291732.1
SRR	XM_006721565.4	c.-5+2128G>T		intron_variant	Intron 1 of 7		XP_006721628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRR	ENST00000344595.10	c.-5+1588G>T		intron_variant	Intron 1 of 7	1	NM_021947.3	ENSP00000339435.5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83403 AN: 151976 Hom.: 24210 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.549 AC: 83446 AN: 152094 Hom.: 24219 Cov.: 32 AF XY: 0.552 AC XY: 41003 AN XY: 74334

African (AFR) AF: 0.349 AC: 14474 AN: 41496

American (AMR) AF: 0.600 AC: 9179 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3472

East Asian (EAS) AF: 0.688 AC: 3558 AN: 5170

South Asian (SAS) AF: 0.553 AC: 2665 AN: 4818

European-Finnish (FIN) AF: 0.624 AC: 6592 AN: 10568

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42699 AN: 67954

Other (OTH) AF: 0.566 AC: 1197 AN: 2116

Alfa AF: 0.613 Hom.: 41368

Bravo AF: 0.539

Asia WGS AF: 0.562 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.64
PhyloP100		0.010
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: rs4523957; hg19: chr17-2208899;