chr11-71527488-C-T

Variant names:

• chr11-71527488-C-T
• rs747759966
• NM_001012503.2:c.188C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001012503.2(KRTAP5-7):​c.188C>T​(p.Ser63Phe) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP5-7 NM_001012503.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.995

Genes affected

KRTAP5-7 (HGNC:23602): (keratin associated protein 5-7) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08571532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-7	NM_001012503.2	c.188C>T	p.Ser63Phe	missense_variant	Exon 1 of 1	ENST00000398536.6	NP_001012521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-7	ENST00000398536.6	c.188C>T	p.Ser63Phe	missense_variant	Exon 1 of 1	6	NM_001012503.2	ENSP00000417330.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.0000485 AC: 12 AN: 247342 Hom.: 0 AF XY: 0.0000671 AC XY: 9 AN XY: 134034

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000263

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000207 AC: 29 AN: 1398184 Hom.: 0 Cov.: 142 AF XY: 0.0000273 AC XY: 19 AN XY: 695968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000261

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000284

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ExAC AF: 0.0000338 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.188C>T (p.S63F) alteration is located in exon 1 (coding exon 1) of the KRTAP5-7 gene. This alteration results from a C to T substitution at nucleotide position 188, causing the serine (S) at amino acid position 63 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.6	H
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.13
Sift	Uncertain	0.017	D
Sift4G	Benign	0.14	T
Polyphen		0.62	P
Vest4		0.16
MutPred		0.20		Loss of glycosylation at S63 (P = 0.0093);
MVP		0.055
MPC		0.011
ClinPred		0.091	T
GERP RS		-4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.076
gMVP		0.014

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: rs747759966; hg19: chr11-71238534;