rs754302660

Variant names:

• chr21-30747103-C-A
• rs754302660
• NM_181617.3:c.100G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-30747103-C-A
• chr21-30747103-C-T

Variant summary

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

The NM_181617.3(KRTAP21-2):​c.100G>T​(p.Gly34Cys) 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. G34S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP21-2 NM_181617.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 0 publications found

Genes affected

KRTAP21-2 (HGNC:18946): (keratin associated protein 21-2) 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=0.13946101).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181617.3. 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
	KRTAP21-2	NM_181617.3	MANE Select	c.100G>T	p.Gly34Cys	missense	Exon 1 of 1	NP_853648.1	Q3LI59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP21-2	ENST00000333892.3	TSL:6 MANE Select	c.100G>T	p.Gly34Cys	missense	Exon 1 of 1	ENSP00000334287.2	Q3LI59

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.75
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.045
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.028
Sift	Benign	0.15	T
Sift4G	Benign	0.10	T
Polyphen		0.38	B
Vest4		0.52
MutPred		0.18		Gain of sheet (P = 0.0477)
MVP		0.076
MPC		0.26
ClinPred		0.24	T
GERP RS		0.37
PromoterAI		-0.00040	Neutral
Varity_R		0.19
gMVP		0.22
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: rs754302660; hg19: chr21-32119421; COSMIC: COSV100441102; COSMIC: COSV100441102;