rs747759966

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 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. 14/21 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08571532).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012503.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-7	NM_001012503.2	MANE Select	c.188C>T	p.Ser63Phe	missense	Exon 1 of 1	NP_001012521.1	Q6L8G8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-7	ENST00000398536.6	TSL:6 MANE Select	c.188C>T	p.Ser63Phe	missense	Exon 1 of 1	ENSP00000417330.2	Q6L8G8

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.0000485 AC: 12 AN: 247342 AF XY: 0.0000671

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33250

American (AMR) AF: 0.0000227 AC: 1 AN: 44040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25366

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.000261 AC: 22 AN: 84366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50496

Middle Eastern (MID) AF: 0.000200 AC: 1 AN: 5012

European-Non Finnish (NFE) AF: 0.00000284 AC: 3 AN: 1057962

Other (OTH) AF: 0.00 AC: 0 AN: 58010

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000338 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.99
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
PromoterAI		0.0051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.076
gMVP		0.014
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs747759966; hg19: chr11-71238534;