5-173235071-G-C

Variant names:

• chr5-173235071-G-C
• NM_004387.4:c.13C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004387.4(NKX2-5):​c.13C>G​(p.Pro5Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,786 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NKX2-5 NM_004387.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08

Genes affected

NKX2-5 (HGNC:2488): (NK2 homeobox 5) This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-5	NM_004387.4	c.13C>G	p.Pro5Ala	missense_variant	Exon 1 of 2	ENST00000329198.5	NP_004378.1
NKX2-5	NM_001166176.2	c.13C>G	p.Pro5Ala	missense_variant	Exon 1 of 2		NP_001159648.1
NKX2-5	NM_001166175.2	c.13C>G	p.Pro5Ala	missense_variant	Exon 1 of 2		NP_001159647.1
NKX2-5	XM_017009071.3	c.13C>G	p.Pro5Ala	missense_variant	Exon 1 of 2		XP_016864560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-5	ENST00000329198.5	c.13C>G	p.Pro5Ala	missense_variant	Exon 1 of 2	1	NM_004387.4	ENSP00000327758.4
NKX2-5	ENST00000424406.2	c.13C>G	p.Pro5Ala	missense_variant	Exon 1 of 2	1		ENSP00000395378.2
NKX2-5	ENST00000521848.1	c.13C>G	p.Pro5Ala	missense_variant	Exon 1 of 2	2		ENSP00000427906.1
NKX2-5	ENST00000517440.1	c.13C>G	p.Pro5Ala	missense_variant	Exon 1 of 2	4		ENSP00000429905.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454786 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723696

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D;.;.;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.1	M;M;M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.8	D;D;D;D
REVEL	Uncertain	0.47
Sift	Benign	0.051	T;T;T;T
Sift4G	Benign	0.070	T;T;T;.
Polyphen		0.079	B;.;.;B
Vest4		0.19
MutPred		0.38		Loss of glycosylation at P5 (P = 0.0219);Loss of glycosylation at P5 (P = 0.0219);Loss of glycosylation at P5 (P = 0.0219);Loss of glycosylation at P5 (P = 0.0219);
MVP		0.84
MPC		1.4
ClinPred		0.94	D
GERP RS		3.9
Varity_R		0.22
gMVP		0.57

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: chr5-172662074;