rs4523957

Positions:

• chr17-2305605-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SRR	NM_021947.3	c.-5+1588G>T		intron_variant		ENST00000344595.10	NP_068766.1
SRR	NM_001304803.1	c.-280+1588G>T		intron_variant			NP_001291732.1
SRR	XM_006721565.4	c.-5+2128G>T		intron_variant			XP_006721628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRR	ENST00000344595.10	c.-5+1588G>T		intron_variant		1	NM_021947.3	ENSP00000339435	P1

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

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.566

Alfa AF: 0.593 Hom.: 6103

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

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: rs4523957; hg19: chr17-2208899;