rs143039156

Variant names:

• chr8-23702971-G-A
• rs143039156
• NM_001136271.3:c.386C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-23702971-G-A
• chr8-23702971-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136271.3(NKX2-6):​c.386C>T​(p.Ala129Val) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A129E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NKX2-6 NM_001136271.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 0 publications found

Genes affected

NKX2-6 (HGNC:32940): (NK2 homeobox 6) This gene encodes a homeobox-containing protein that belongs to the NK-2 homeobox family. This protein is a vertebrate homolog of Drosophila homeobox-containing protein called 'tinman', which has been shown to be essential for development of the heart-like dorsal vessel. In conjunction with related gene, NKX2-5, this gene may play a role in both pharyngeal and cardiac embryonic development. Mutations in this gene are associated with persistent truncus arteriosus.[provided by RefSeq, Aug 2011]

NKX2-6 Gene-Disease associations (from GenCC):

• conotruncal heart malformations

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital heart disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

LOC107986930 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06760946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-6	NM_001136271.3	c.386C>T	p.Ala129Val	missense_variant	Exon 2 of 2	ENST00000325017.4	NP_001129743.2
LOC107986930	XR_001745842.2	n.1312+34221G>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-6	ENST00000325017.4	c.386C>T	p.Ala129Val	missense_variant	Exon 2 of 2	2	NM_001136271.3	ENSP00000320089.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.18	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.068	T
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.010
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.28
Sift	Benign	0.24	T
Sift4G	Benign	0.27	T
Polyphen		0.79	P
Vest4		0.051
MutPred		0.22		Gain of methylation at K128 (P = 0.0354);
MVP		0.49
MPC		0.45
ClinPred		0.14	T
GERP RS		-2.0
Varity_R		0.035
gMVP		0.32
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143039156; hg19: chr8-23560484;