Variant 12-25108768-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018272.5(DNAI7):c.1949T>C(p.Met650Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00123 in 1,510,210 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

DNAI7
NM_018272.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30

Variant links:

Genes affected

DNAI7 (HGNC:29599): (dynein axonemal intermediate chain 7) Predicted to enable beta-tubulin binding activity and microtubule binding activity. Predicted to be located in cilium; cytoplasm; and microtubule cytoskeleton. Predicted to be part of axonemal dynein complex. Predicted to be active in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

DNAI7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11917478).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI7	NM_018272.5 linkuse as main transcript	c.1949T>C	p.Met650Thr	missense_variant	16/16	ENST00000395987.8	NP_060742.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI7	ENST00000395987.8 linkuse as main transcript	c.1949T>C	p.Met650Thr	missense_variant	16/16	1	NM_018272.5	ENSP00000379310	A1

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

139532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000826

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:

0.000908

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000518

AC:

129

AN:

248928

Hom.:

AF XY:

0.000490

AC XY:

AN XY:

134686

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000955

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.00131

AC:

1795

AN:

1370556

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

857

AN XY:

682320

show subpopulations

Gnomad4 AFR exome

AF:

0.0000928

Gnomad4 AMR exome

AF:

0.000188

Gnomad4 ASJ exome

AF:

0.0000433

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000642

Gnomad4 NFE exome

AF:

0.00166

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000480

AC:

AN:

139654

Hom.:

Cov.:

AF XY:

0.000495

AC XY:

AN XY:

66614

show subpopulations

Gnomad4 AFR

AF:

0.000177

Gnomad4 AMR

AF:

0.0000825

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000908

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.000635

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000552

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2024

The c.1949T>C (p.M650T) alteration is located in exon 16 (coding exon 16) of the CASC1 gene. This alteration results from a T to C substitution at nucleotide position 1949, causing the methionine (M) at amino acid position 650 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.14

T;D;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.7

.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.8

D;D;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0070

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.96

D;P;.;.

Vest4

0.47

MVP

0.73

MPC

0.34

ClinPred

0.20

GERP RS

5.6

Varity_R

0.49

gMVP

0.56

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over