11-71527716-C-T

Variant names:

• chr11-71527716-C-T
• rs765423098
• NM_001012503.2:c.416C>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.416C>T​(p.Ser139Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000832 in 1,201,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. S139C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: KRTAP5-7 NM_001012503.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 1 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=0.07157084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-7	NM_001012503.2	c.416C>T	p.Ser139Phe	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.416C>T	p.Ser139Phe	missense_variant	Exon 1 of 1	6	NM_001012503.2	ENSP00000417330.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249894 AF XY: 0.00000740

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.32e-7 AC: 1 AN: 1201382 Hom.: 0 Cov.: 35 AF XY: 0.00000166 AC XY: 1 AN XY: 601374

African (AFR) AF: 0.00 AC: 0 AN: 28704

American (AMR) AF: 0.00 AC: 0 AN: 43152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24282

East Asian (EAS) AF: 0.00 AC: 0 AN: 38146

South Asian (SAS) AF: 0.00 AC: 0 AN: 79416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4994

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 882792

Other (OTH) AF: 0.00 AC: 0 AN: 51924

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.73
DEOGEN2	Benign	0.037	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.024	T
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		-1.2
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.080
Sift	Benign	0.042	D
Sift4G	Uncertain	0.012	D
Polyphen		0.049	B
Vest4		0.15
MutPred		0.22		Gain of catalytic residue at S139 (P = 0.0557);
MVP		0.043
MPC		0.011
ClinPred		0.17	T
GERP RS		-3.1
PromoterAI		-0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.082
gMVP		0.012
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs765423098; hg19: chr11-71238762;