22-24568160-T-C

Variant names:

• chr22-24568160-T-C
• rs4597
• NM_004175.5:c.303T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004175.5(SNRPD3):​c.303T>C​(p.Ala101Ala) 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
• Publications: 24 publications found

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]

ENSG00000286070 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004175.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPD3	NM_004175.5	MANE Select	c.303T>C	p.Ala101Ala	synonymous	Exon 3 of 4	NP_004166.1	P62318-1
	SNRPD3	NM_001278656.2		c.303T>C	p.Ala101Ala	synonymous	Exon 3 of 4	NP_001265585.1	P62318-1
	SNRPD3	NR_103819.1		n.567-3756T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPD3	ENST00000215829.8	TSL:1 MANE Select	c.303T>C	p.Ala101Ala	synonymous	Exon 3 of 4	ENSP00000215829.3	P62318-1
	ENSG00000286070	ENST00000652248.1		n.303T>C		non_coding_transcript_exon	Exon 3 of 20	ENSP00000499210.1
	SNRPD3	ENST00000940751.1		c.321T>C	p.Ala107Ala	synonymous	Exon 3 of 4	ENSP00000610810.1

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

GnomAD2 exomes AF: 0.790 AC: 197719 AN: 250302 AF XY: 0.790

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 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

African (AFR) AF: 0.473 AC: 15797 AN: 33366

American (AMR) AF: 0.798 AC: 35436 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 21008 AN: 26096

East Asian (EAS) AF: 0.787 AC: 31218 AN: 39676

South Asian (SAS) AF: 0.672 AC: 57887 AN: 86112

European-Finnish (FIN) AF: 0.850 AC: 45365 AN: 53398

Middle Eastern (MID) AF: 0.782 AC: 4504 AN: 5756

European-Non Finnish (NFE) AF: 0.845 AC: 939399 AN: 1111206

Other (OTH) AF: 0.800 AC: 48255 AN: 60328

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

African (AFR) AF: 0.490 AC: 20306 AN: 41456

American (AMR) AF: 0.765 AC: 11691 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2805 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4401 AN: 5182

South Asian (SAS) AF: 0.637 AC: 3071 AN: 4818

European-Finnish (FIN) AF: 0.853 AC: 9034 AN: 10588

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57097 AN: 67994

Other (OTH) AF: 0.761 AC: 1608 AN: 2112

Alfa AF: 0.808 Hom.: 102146

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.56
PhyloP100		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs4597; hg19: chr22-24964128; COSMIC: COSV53182827;