rs771961191

Variant names:

• chr4-13542066-G-A
• rs771961191
• NM_001189.4:c.929C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-13542066-G-A
• chr4-13542066-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001189.4(NKX3-2):​c.929C>T​(p.Ser310Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,455,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: NKX3-2 NM_001189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38

Genes affected

NKX3-2 (HGNC:951): (NK3 homeobox 2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; negative regulation of chondrocyte differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including animal organ development; embryonic skeletal system development; and intestinal epithelial cell development. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX3-2	NM_001189.4	c.929C>T	p.Ser310Phe	missense_variant	Exon 2 of 2	ENST00000382438.6	NP_001180.1
NKX3-2	XM_047416049.1	c.929C>T	p.Ser310Phe	missense_variant	Exon 3 of 3		XP_047272005.1
NKX3-2	XM_047416050.1	c.929C>T	p.Ser310Phe	missense_variant	Exon 3 of 3		XP_047272006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX3-2	ENST00000382438.6	c.929C>T	p.Ser310Phe	missense_variant	Exon 2 of 2	1	NM_001189.4	ENSP00000371875.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000127 AC: 3 AN: 237048 Hom.: 0 AF XY: 0.0000233 AC XY: 3 AN XY: 129010

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1455452 Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4 AN XY: 723264

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: 0.0000586

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.68
MutPred		0.56		Loss of disorder (P = 0.036);
MVP		0.97
MPC		1.1
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.37
gMVP		0.85

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: rs771961191; hg19: chr4-13543690;