10-99535094-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_145285.3(NKX2-3):c.468G>A(p.Ser156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,609,354 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (18 hom.)
• Consequence: NKX2-3 NM_145285.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44

Genes affected

NKX2-3 (HGNC:7836): (NK2 homeobox 3) This gene encodes a homeodomain-containing transcription factor. The encoded protein is a member of the NKX family of homeodomain transcription factors. Studies of similar proteins in mouse and rat have indicated a potential role in cellular differentiation.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 10-99535094-G-A is Benign according to our data. Variant chr10-99535094-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.44 with no splicing effect.
• BS2: High AC in GnomAd at 565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKX2-3	NM_145285.3	c.468G>A	p.Ser156=	synonymous_variant	2/2	ENST00000344586.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX2-3	ENST00000344586.9	c.468G>A	p.Ser156=	synonymous_variant	2/2	2	NM_145285.3	P1

Frequencies

GnomAD3 genomes AF: 0.00371 AC: 565 AN: 152236 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00614

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00386 AC: 918 AN: 237608 Hom.: 4 AF XY: 0.00383 AC XY: 497 AN XY: 129660

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00215

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00183

Gnomad FIN exome AF: 0.00417

Gnomad NFE exome AF: 0.00637

Gnomad OTH exome AF: 0.00292

GnomAD4 exome AF: 0.00464 AC: 6755 AN: 1457000 Hom.: 18 Cov.: 34 AF XY: 0.00455 AC XY: 3294 AN XY: 724342

Gnomad4 AFR exome AF: 0.000928

Gnomad4 AMR exome AF: 0.00133

Gnomad4 ASJ exome AF: 0.00212

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00159

Gnomad4 FIN exome AF: 0.00351

Gnomad4 NFE exome AF: 0.00544

Gnomad4 OTH exome AF: 0.00379

GnomAD4 genome AF: 0.00371 AC: 565 AN: 152354 Hom.: 3 Cov.: 33 AF XY: 0.00360 AC XY: 268 AN XY: 74496

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.00614

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.00337

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

NKX2-3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	7.9
Dann	Benign	0.96

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: rs184601313; hg19: chr10-101294851;