rs113068438

Positions:

• chr20-62475514-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_080473.5(GATA5):​c.8A>G​(p.Gln3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00684 in 1,318,038 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (47 hom.)
• Consequence: GATA5 NM_080473.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.25

Genes affected

GATA5 (HGNC:15802): (GATA binding protein 5) The protein encoded by this gene is a transcription factor that contains two GATA-type zinc fingers. The encoded protein is known to bind to hepatocyte nuclear factor-1alpha (HNF-1alpha), and this interaction is essential for cooperative activation of the intestinal lactase-phlorizin hydrolase promoter. In other organisms, similar proteins may be involved in the establishment of cardiac smooth muscle cell diversity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0130209625).
• BP6: Variant 20-62475514-T-C is Benign according to our data. Variant chr20-62475514-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 180366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62475514-T-C is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 683 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA5	NM_080473.5	c.8A>G	p.Gln3Arg	missense_variant	2/7	ENST00000252997.3	NP_536721.1
GATA5	XM_006723699.3	c.8A>G	p.Gln3Arg	missense_variant	2/7		XP_006723762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA5	ENST00000252997.3	c.8A>G	p.Gln3Arg	missense_variant	2/7	1	NM_080473.5	ENSP00000252997.2

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 683 AN: 152098 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00716

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00766

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00581 AC: 261 AN: 44910 Hom.: 4 AF XY: 0.00580 AC XY: 152 AN XY: 26226

Gnomad AFR exome AF: 0.000754

Gnomad AMR exome AF: 0.000504

Gnomad ASJ exome AF: 0.00472

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000852

Gnomad FIN exome AF: 0.00990

Gnomad NFE exome AF: 0.00876

Gnomad OTH exome AF: 0.00381

GnomAD4 exome AF: 0.00714 AC: 8326 AN: 1165824 Hom.: 47 Cov.: 32 AF XY: 0.00691 AC XY: 3884 AN XY: 562400

Gnomad4 AFR exome AF: 0.000865

Gnomad4 AMR exome AF: 0.000681

Gnomad4 ASJ exome AF: 0.00128

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000292

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.00796

Gnomad4 OTH exome AF: 0.00454

GnomAD4 genome AF: 0.00449 AC: 683 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.00402 AC XY: 299 AN XY: 74426

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00716

Gnomad4 NFE AF: 0.00766

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00522 Hom.: 0

Bravo AF: 0.00377

ESP6500AA AF: 0.000741 AC: 2

ESP6500EA AF: 0.00439 AC: 27

ExAC AF: 0.00398 AC: 423

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	GATA5: PP2, PP3, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 23, 2018	This variant is associated with the following publications: (PMID: 23040494, 24796370, 22641149) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Likely benign, no assertion criteria provided

clinical testing

Blueprint Genetics

Jul 03, 2014

- -

GATA5-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.95	D
Eigen	Benign	0.13
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.013	T
MetaSVM	Uncertain	0.70	D
MutationAssessor	Uncertain	2.9	M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.56
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.89	P
Vest4		0.34
MVP		0.94
MPC		1.7
ClinPred		0.062	T
GERP RS		1.3
Varity_R		0.040
gMVP		0.63

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: rs113068438; hg19: chr20-61050570;