rs12053975

chr3-57352120-C-Gchr3-57352120-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001366028.2(DNAH12):c.9639G>C(p.Leu3213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,527,738 control chromosomes in the GnomAD database, including 45,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4503 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40536 hom.)
• Consequence: DNAH12 NM_001366028.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.183

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-57352120-C-G is Benign according to our data. Variant chr3-57352120-C-G is described in ClinVar as [Benign]. Clinvar id is 402631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH12	NM_001366028.2	c.9639G>C	p.Leu3213=	synonymous_variant	60/74	ENST00000495027.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH12	ENST00000495027.6	c.9639G>C	p.Leu3213=	synonymous_variant	60/74	5	NM_001366028.2	P1
DNAH12	ENST00000351747.6	c.7035G>C	p.Leu2345=	synonymous_variant	45/59	5
DNAH12	ENST00000466540.2	c.117G>C	p.Leu39=	synonymous_variant	2/15	5

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34195 AN: 151848 Hom.: 4501 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.278 AC: 38176 AN: 137390 Hom.: 5786 AF XY: 0.282 AC XY: 20507 AN XY: 72688

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.326

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.381

Gnomad SAS exome AF: 0.369

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.233 AC: 321213 AN: 1375770 Hom.: 40536 Cov.: 32 AF XY: 0.238 AC XY: 161343 AN XY: 677544

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.225 AC: 34207 AN: 151968 Hom.: 4503 Cov.: 32 AF XY: 0.235 AC XY: 17485 AN XY: 74260

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.235

Alfa AF: 0.236 Hom.: 1477

Bravo AF: 0.216

Asia WGS AF: 0.427 AC: 1476 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	1.2
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs12053975; hg19: chr3-57386148; COSMIC: COSV61063437;