rs6773904

Positions:

• chr3-57433770-C-G
• chr3-57433770-C-T

Variant summary

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

The NM_001366028.2(DNAH12):​c.4714G>C​(p.Asp1572His) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,398,672 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAH12 NM_001366028.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07

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.4714G>C	p.Asp1572His	missense_variant	31/74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.4714G>C	p.Asp1572His	missense_variant	31/74	5	NM_001366028.2	ENSP00000418137	P1
DNAH12	ENST00000351747.6	c.4645G>C	p.Asp1549His	missense_variant	31/59	5		ENSP00000295937

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398672 Hom.: 0 Cov.: 46 AF XY: 0.00000145 AC XY: 1 AN XY: 689804

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.030	T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.6	.;L
MutationTaster	Benign	0.10	P
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.30
Sift	Benign	0.13	T;T
Polyphen		1.0	.;D
Vest4		0.28
MutPred		0.35		.;Gain of catalytic residue at L1551 (P = 0.1012);
MVP		0.75
ClinPred		0.74	D
GERP RS		4.9
Varity_R		0.20

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: rs6773904; hg19: chr3-57419497;