NM_021167.5:c.70G>C

Variant names:

• chr7-92447799-G-C
• NM_021167.5:c.70G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_021167.5(GATAD1):​c.70G>C​(p.Ala24Pro) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GATAD1 NM_021167.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.754

Genes affected

GATAD1 (HGNC:29941): (GATA zinc finger domain containing 1) The protein encoded by this gene contains a zinc finger at the N-terminus, and is thought to bind to a histone modification site that regulates gene expression. Mutations in this gene have been associated with autosomal recessive dilated cardiomyopathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

TMBIM7P (HGNC:49212): (transmembrane BAX inhibitor motif containing 7, pseudogene)

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=0.09236857).
• BP6: Variant 7-92447799-G-C is Benign according to our data. Variant chr7-92447799-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3519087.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD1	NM_021167.5	c.70G>C	p.Ala24Pro	missense_variant	Exon 1 of 5	ENST00000287957.5	NP_066990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD1	ENST00000287957.5	c.70G>C	p.Ala24Pro	missense_variant	Exon 1 of 5	1	NM_021167.5	ENSP00000287957.3
TMBIM7P	ENST00000641474.1	n.15C>G		non_coding_transcript_exon_variant	Exon 1 of 10
GATAD1	ENST00000645746.1	n.70G>C		non_coding_transcript_exon_variant	Exon 1 of 6			ENSP00000493785.1
GATAD1	ENST00000644160.1	n.-75G>C		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Benign:1

Oct 21, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.00062	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.092	T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	-1.3	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.56	N
REVEL	Uncertain	0.29
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.088
MutPred		0.31		Loss of helix (P = 0.0444);
MVP		0.14
MPC		0.39
ClinPred		0.065	T
GERP RS		-0.17
Varity_R		0.096
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-92077113;