rs1020773811

Variant names:

• chr21-30396214-C-G
• rs1020773811
• NM_181599.3:c.128C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-30396214-C-G
• chr21-30396214-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_181599.3(KRTAP13-1):​c.128C>G​(p.Pro43Arg) 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 pathogenic 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. P43L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP13-1 NM_181599.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 0 publications found

Genes affected

KRTAP13-1 (HGNC:18924): (keratin associated protein 13-1) Hair keratins and hair keratin-associated proteins (KAPs), such as KRTAP13-1, are the main structural proteins of hair fibers (Rogers et al., 2002 [PubMed 12359730]).[supplied by OMIM, Mar 2008]

LOC105372772 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.961

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181599.3. 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
	KRTAP13-1	NM_181599.3	MANE Select	c.128C>G	p.Pro43Arg	missense	Exon 1 of 1	NP_853630.2	Q8IUC0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP13-1	ENST00000355459.4	TSL:6 MANE Select	c.128C>G	p.Pro43Arg	missense	Exon 1 of 1	ENSP00000347635.2	Q8IUC0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.83
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.022	D
Polyphen		0.24	B
Vest4		0.65
MutPred		0.91		Gain of catalytic residue at P43 (P = 0.0643)
MVP		0.59
MPC		0.63
ClinPred		0.60	D
GERP RS		3.6
PromoterAI		-0.0016	Neutral
Varity_R		0.23
gMVP		0.17
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1020773811; hg19: chr21-31768532;