rs11915740

Variant names:

• chr3-57428603-C-A
• rs11915740
• NM_001366028.2:c.5253+30G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366028.2(DNAH12):​c.5253+30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,510,268 control chromosomes in the GnomAD database, including 124,691 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 0.32 (8780 hom., cov: 32)
  • Exomes 𝑓: 0.40 (115911 hom.)
• Consequence: DNAH12 NM_001366028.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 8 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=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366028.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH12	NM_001366028.2	MANE Select	c.5253+30G>T		intron	N/A	NP_001352957.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH12	ENST00000495027.6	TSL:5 MANE Select	c.5253+30G>T		intron	N/A	ENSP00000418137.2
	DNAH12	ENST00000351747.6	TSL:5	c.5167+47G>T		intron	N/A	ENSP00000295937.3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48103 AN: 151956 Hom.: 8787 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.0761

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.340

GnomAD2 exomes AF: 0.350 AC: 42821 AN: 122252 AF XY: 0.356

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.409

Gnomad EAS exome AF: 0.0657

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.405 AC: 549481 AN: 1358194 Hom.: 115911 Cov.: 31 AF XY: 0.404 AC XY: 269734 AN XY: 667228

African (AFR) AF: 0.149 AC: 4355 AN: 29286

American (AMR) AF: 0.241 AC: 5907 AN: 24478

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 9478 AN: 23168

East Asian (EAS) AF: 0.0804 AC: 2838 AN: 35318

South Asian (SAS) AF: 0.369 AC: 26738 AN: 72420

European-Finnish (FIN) AF: 0.401 AC: 19503 AN: 48670

Middle Eastern (MID) AF: 0.388 AC: 2135 AN: 5498

European-Non Finnish (NFE) AF: 0.430 AC: 457385 AN: 1063226

Other (OTH) AF: 0.377 AC: 21142 AN: 56130

GnomAD4 genome AF: 0.316 AC: 48121 AN: 152074 Hom.: 8780 Cov.: 32 AF XY: 0.313 AC XY: 23243 AN XY: 74328

African (AFR) AF: 0.155 AC: 6432 AN: 41504

American (AMR) AF: 0.256 AC: 3907 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1431 AN: 3470

East Asian (EAS) AF: 0.0761 AC: 394 AN: 5180

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4818

European-Finnish (FIN) AF: 0.401 AC: 4235 AN: 10562

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28872 AN: 67942

Other (OTH) AF: 0.335 AC: 709 AN: 2114

Alfa AF: 0.389 Hom.: 52702

Bravo AF: 0.298

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		-0.90
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: rs11915740; hg19: chr3-57414330; COSMIC: COSV61058983;