3-57313850-C-T

Position:

• chr3-57313850-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366028.2(DNAH12):​c.10662+644G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,998 control chromosomes in the GnomAD database, including 10,459 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 0.33 (10459 hom., cov: 31)
• Consequence: DNAH12 NM_001366028.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

Genes affected

DNAH12 (HGNC:2943): (dynein axonemal heavy chain 12) Predicted to enable several functions, including ATP binding activity; dynein intermediate chain binding activity; and dynein light intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in cilium; cytoplasm; and microtubule. Predicted to be part of dynein complex. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.10662+644G>A		intron_variant		ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.10662+644G>A		intron_variant		5	NM_001366028.2	ENSP00000418137	P1
DNAH12	ENST00000351747.6	c.8058+644G>A		intron_variant		5		ENSP00000295937
DNAH12	ENST00000466540.2	c.1002-2900G>A		intron_variant		5		ENSP00000420359

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50336 AN: 151880 Hom.: 10440 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.331 AC: 50367 AN: 151998 Hom.: 10459 Cov.: 31 AF XY: 0.343 AC XY: 25490 AN XY: 74284

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.351

Alfa AF: 0.349 Hom.: 19789

Bravo AF: 0.331

Asia WGS AF: 0.677 AC: 2351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.0
DANN	Benign	0.79

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: rs571879; hg19: chr3-57347878;