22-24568160-T-C

Position:

• chr22-24568160-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004175.5(SNRPD3):​c.303T>C​(p.Ala101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,612,462 control chromosomes in the GnomAD database, including 538,545 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 0.73 (42284 hom., cov: 32)
  • Exomes 𝑓: 0.82 (496261 hom.)
• Consequence: SNRPD3 NM_004175.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426

Genes affected

SNRPD3 (HGNC:11160): (small nuclear ribonucleoprotein D3 polypeptide) This gene encodes a core component of the spliceosome, which is a nuclear ribonucleoprotein complex that functions in pre-mRNA splicing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.426 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRPD3	NM_004175.5	c.303T>C	p.Ala101=	synonymous_variant	3/4	ENST00000215829.8
SNRPD3	NM_001278656.2	c.303T>C	p.Ala101=	synonymous_variant	3/4
SNRPD3	NR_103819.1	n.567-3756T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPD3	ENST00000215829.8	c.303T>C	p.Ala101=	synonymous_variant	3/4	1	NM_004175.5	P1
SNRPD3	ENST00000402849.5	c.303T>C	p.Ala101=	synonymous_variant	3/5	2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110899 AN: 151986 Hom.: 42272 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.762

GnomAD3 exomes AF: 0.790 AC: 197719 AN: 250302 Hom.: 79450 AF XY: 0.790 AC XY: 106884 AN XY: 135316

Gnomad AFR exome AF: 0.485

Gnomad AMR exome AF: 0.802

Gnomad ASJ exome AF: 0.804

Gnomad EAS exome AF: 0.850

Gnomad SAS exome AF: 0.668

Gnomad FIN exome AF: 0.849

Gnomad NFE exome AF: 0.840

Gnomad OTH exome AF: 0.801

GnomAD4 exome AF: 0.821 AC: 1198869 AN: 1460358 Hom.: 496261 Cov.: 39 AF XY: 0.818 AC XY: 594012 AN XY: 726498

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.798

Gnomad4 ASJ exome AF: 0.805

Gnomad4 EAS exome AF: 0.787

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.850

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.729 AC: 110943 AN: 152104 Hom.: 42284 Cov.: 32 AF XY: 0.727 AC XY: 54044 AN XY: 74346

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.761

Alfa AF: 0.818 Hom.: 74449

Bravo AF: 0.721

Asia WGS AF: 0.701 AC: 2439 AN: 3478

EpiCase AF: 0.825

EpiControl AF: 0.832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs4597; hg19: chr22-24964128; COSMIC: COSV53182827;