rs4060726

Positions:

• chr3-57301848-C-A
• chr3-57301848-C-G
• chr3-57301848-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366028.2(DNAH12):​c.11281G>T​(p.Gly3761Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DNAH12 NM_001366028.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.11281G>T	p.Gly3761Cys	missense_variant	70/74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.11281G>T	p.Gly3761Cys	missense_variant	70/74	5	NM_001366028.2	ENSP00000418137.2
DNAH12	ENST00000351747.6	c.8677G>T	p.Gly2893Cys	missense_variant	55/59	5		ENSP00000295937.3
DNAH12	ENST00000466540.2	c.1618G>T	p.Gly540Cys	missense_variant	11/15	5		ENSP00000420359.2
DNAH12	ENST00000494758.5	n.96-4864G>T		intron_variant		2		ENSP00000420717.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.85	D;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.1	.;D
REVEL	Benign	0.20
Sift	Benign	0.041	.;D
Polyphen		1.0	.;D
Vest4		0.40
MutPred		0.54		.;Loss of disorder (P = 0.0659);
MVP		0.28
ClinPred		0.98	D
GERP RS		2.3
Varity_R		0.50

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: rs4060726; hg19: chr3-57335876;