rs549251713

Variant names:

• chr17-41139934-T-A
• NM_030976.2:c.554A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41139934-T-A
• chr17-41139934-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030976.2(KRTAP4-6):​c.554A>T​(p.Tyr185Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Y185C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 37)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KRTAP4-6 NM_030976.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

Genes affected

KRTAP4-6 (HGNC:18909): (keratin associated protein 4-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093292415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-6	NM_030976.2	c.554A>T	p.Tyr185Phe	missense_variant	Exon 1 of 1	ENST00000345847.5	NP_112238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-6	ENST00000345847.5	c.554A>T	p.Tyr185Phe	missense_variant	Exon 1 of 1	6	NM_030976.2	ENSP00000328270.5

Frequencies

GnomAD3 genomes Cov.: 37

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453808 Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0 AN XY: 722324

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 37

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.42
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.061	T
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.037
Sift	Benign	0.058	T
Sift4G	Benign	0.13	T
Vest4		0.36
MutPred		0.38		Gain of sheet (P = 0.1539);
MVP		0.048
MPC		0.051
ClinPred		0.20	T
GERP RS		0.80
Varity_R		0.15
gMVP		0.087

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: chr17-39296186;