KRTAP11-1 p.Cys56Ser

Variant names:

• chr21-30881358-C-G
• NM_175858.3:c.167G>C
• KRTAP11-1 p.Cys56Ser

Your query was ambiguous. Multiple possible variants found:

• chr21-30881358-C-G
• chr21-30881359-A-T
• chr21-30881357-AC-GG
• chr21-30881357-AC-TG
• chr21-30881357-AC-CG
• chr21-30881357-ACA-GCT

Variant summary

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

The NM_175858.3(KRTAP11-1):​c.167G>C​(p.Cys56Ser) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP11-1 NM_175858.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48
• Publications: 0 publications found

Genes affected

KRTAP11-1 (HGNC:18922): (keratin associated protein 11-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.968

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175858.3. 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
	KRTAP11-1	NM_175858.3	MANE Select	c.167G>C	p.Cys56Ser	missense	Exon 1 of 1	NP_787054.1	Q8IUC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP11-1	ENST00000332378.6	TSL:6 MANE Select	c.167G>C	p.Cys56Ser	missense	Exon 1 of 1	ENSP00000330720.4	Q8IUC1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-1.2	T
PhyloP100		3.5
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-8.9	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.011	D
Sift4G	Benign	0.098	T
PromoterAI		0.0065	Neutral
Varity_R		0.61
gMVP		0.45
Mutation Taster		=70/30	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-32253677;