3-57313850-C-T

Variant names:

• chr3-57313850-C-T
• rs571879
• NM_001366028.2:c.10662+644G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

DNAH12 Gene-Disease associations (from GenCC):

• oligoasthenoteratozoospermia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.10662+644G>A		intron_variant	Intron 66 of 73	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.10662+644G>A		intron_variant	Intron 66 of 73	5	NM_001366028.2	ENSP00000418137.2
DNAH12	ENST00000351747.6	c.8058+644G>A		intron_variant	Intron 51 of 58	5		ENSP00000295937.3
DNAH12	ENST00000466540.2	c.1000-2900G>A		intron_variant	Intron 7 of 14	5		ENSP00000420359.2

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

African (AFR) AF: 0.144 AC: 5977 AN: 41480

American (AMR) AF: 0.486 AC: 7419 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1730 AN: 3468

East Asian (EAS) AF: 0.922 AC: 4755 AN: 5156

South Asian (SAS) AF: 0.522 AC: 2512 AN: 4816

European-Finnish (FIN) AF: 0.386 AC: 4069 AN: 10536

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22633 AN: 67958

Other (OTH) AF: 0.351 AC: 743 AN: 2114

Alfa AF: 0.346 Hom.: 27653

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
PhyloP100		0.27
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: rs571879; hg19: chr3-57347878;