chr11-71548764-G-C

Variant names:

• chr11-71548764-G-C
• rs1345492519
• NM_005553.4:c.107G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005553.4(KRTAP5-9):​c.107G>C​(p.Cys36Ser) 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. 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. C36Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRTAP5-9 NM_005553.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 0 publications found

Genes affected

KRTAP5-9 (HGNC:23604): (keratin associated protein 5-9) Enables identical protein binding activity. Predicted to be involved in epidermis development. 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=0.19797179).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005553.4. 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
	KRTAP5-9	NM_005553.4	MANE Select	c.107G>C	p.Cys36Ser	missense	Exon 1 of 1	NP_005544.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-9	ENST00000528743.4	TSL:6 MANE Select	c.107G>C	p.Cys36Ser	missense	Exon 1 of 1	ENSP00000431443.3	P26371

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.016
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.00069	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		1.6
PROVEAN	Pathogenic	-8.6	D
REVEL	Benign	0.085
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.94	P
Vest4		0.14
MutPred		0.29		Loss of catalytic residue at C36 (P = 0.0895)
MVP		0.62
MPC		0.12
ClinPred		0.48	T
GERP RS		1.5
PromoterAI		0.013	Neutral
Varity_R		0.64
Mutation Taster		=93/7	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: rs1345492519; hg19: chr11-71259810;