NM_001085455.3:c.535C>G

Variant names:

• chr21-30282398-G-C
• rs1017568295
• NM_001085455.3:c.535C>G

Variant summary

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

The NM_001085455.3(KRTAP24-1):​c.535C>G​(p.Gln179Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: KRTAP24-1 NM_001085455.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.366
• Publications: 0 publications found

Genes affected

KRTAP24-1 (HGNC:33902): (keratin associated protein 24-1) Predicted to enable structural molecule activity. 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=0.09178987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085455.3. 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
	KRTAP24-1	NM_001085455.3	MANE Select	c.535C>G	p.Gln179Glu	missense	Exon 1 of 1	NP_001078924.1	Q3LI83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP24-1	ENST00000340345.6	TSL:6 MANE Select	c.535C>G	p.Gln179Glu	missense	Exon 1 of 1	ENSP00000339238.4	Q3LI83

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248972 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000301 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.37
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.092
Sift	Benign	0.32	T
Sift4G	Benign	0.49	T
Polyphen		0.65	P
Vest4		0.26
MVP		0.32
MPC		0.013
ClinPred		0.44	T
GERP RS		4.0
Varity_R		0.060
gMVP		0.077
Mutation Taster		=100/0	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: rs1017568295; hg19: chr21-31654716;