21-30371693-G-C

Variant names:

• chr21-30371693-G-C
• NM_181621.4:c.521C>G
• KRTAP13-2 p.Thr174Ser

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181621.4(KRTAP13-2):​c.521C>G​(p.Thr174Ser) 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. 16/22 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. T174A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRTAP13-2 NM_181621.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

KRTAP13-2 (HGNC:18923): (keratin associated protein 13-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05356452).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181621.4. 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
	KRTAP13-2	NM_181621.4	MANE Select	c.521C>G	p.Thr174Ser	missense	Exon 1 of 1	NP_853652.1	Q52LG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP13-2	ENST00000399889.4	TSL:6 MANE Select	c.521C>G	p.Thr174Ser	missense	Exon 1 of 1	ENSP00000382777.2	Q52LG2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.69
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.41	N
PhyloP100		1.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.038
Sift	Benign	0.27	T
Sift4G	Benign	0.45	T
Varity_R		0.041
gMVP		0.020
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr21-31744011;