Variant 3-57489624-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366028.2(DNAH12):c.1399A>G(p.Thr467Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0 ( 0 hom., cov: 30)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAH12
NM_001366028.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.045711994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH12	NM_001366028.2 linkuse as main transcript	c.1399A>G	p.Thr467Ala	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 linkuse as main transcript	c.1399A>G	p.Thr467Ala	missense_variant	12/74	5	NM_001366028.2	ENSP00000418137	P1
DNAH12	ENST00000351747.6 linkuse as main transcript	c.1399A>G	p.Thr467Ala	missense_variant	12/59	5		ENSP00000295937		Q6ZR08-1
DNAH12	ENST00000389536.8 linkuse as main transcript	c.1399A>G	p.Thr467Ala	missense_variant	12/17	5		ENSP00000374187

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151578

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000691

AC:

AN:

144648

Hom.:

AF XY:

0.0000130

AC XY:

AN XY:

76786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1388978

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684774

show subpopulations

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:

9.30e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151578

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74000

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000359

Hom.:

64536

ExAC

AF:

0.0000428

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0071

T;T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.30

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

.;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

0.27

N;N;N

REVEL

Benign

0.068

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.11

.;.;T

Polyphen

0.0020

.;B;.

Vest4

0.14

MutPred

0.51

Gain of catalytic residue at T467 (P = 0.2156);Gain of catalytic residue at T467 (P = 0.2156);Gain of catalytic residue at T467 (P = 0.2156);

MVP

0.18

ClinPred

0.16

GERP RS

5.4

Varity_R

0.051

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over