rs6806444

Positions:

• chr3-57489624-T-A
• chr3-57489624-T-C
• chr3-57489624-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366028.2(DNAH12):​c.1399A>T​(p.Thr467Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH12 NM_001366028.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05847606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.1399A>T	p.Thr467Ser	missense_variant	12/74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.1399A>T	p.Thr467Ser	missense_variant	12/74	5	NM_001366028.2	ENSP00000418137	P1
DNAH12	ENST00000351747.6	c.1399A>T	p.Thr467Ser	missense_variant	12/59	5		ENSP00000295937
DNAH12	ENST00000389536.8	c.1399A>T	p.Thr467Ser	missense_variant	12/17	5		ENSP00000374187

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1388976 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 684774

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.0073	T;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.16	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	.;N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.62	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.17	.;.;T
Polyphen		0.0050	.;B;.
Vest4		0.14
MutPred		0.53		Gain of catalytic residue at T467 (P = 0.1039);Gain of catalytic residue at T467 (P = 0.1039);Gain of catalytic residue at T467 (P = 0.1039);
MVP		0.18
ClinPred		0.47	T
GERP RS		5.4
Varity_R		0.050

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: rs6806444; hg19: chr3-57475351;