chr21-30718608-A-C

Variant names:

• chr21-30718608-A-C
• rs199854635
• NM_001164435.1:c.152T>G

Variant summary

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

The NM_001164435.1(KRTAP21-3):​c.152T>G​(p.Phe51Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,379,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. F51Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: KRTAP21-3 NM_001164435.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 0 publications found

Genes affected

KRTAP21-3 (HGNC:34216): (keratin associated protein 21-3) Predicted to be located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000295670 (HGNC:):

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=0.1234521).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164435.1. 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
	KRTAP21-3	NM_001164435.1	MANE Select	c.152T>G	p.Phe51Cys	missense	Exon 1 of 1	NP_001157907.1	Q3LHN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP21-3	ENST00000444335.1	TSL:6 MANE Select	c.152T>G	p.Phe51Cys	missense	Exon 1 of 1	ENSP00000404517.1	Q3LHN1
	ENSG00000295670	ENST00000731715.1		n.137+6909T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1379060 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 679620

African (AFR) AF: 0.00 AC: 0 AN: 30410

American (AMR) AF: 0.00 AC: 0 AN: 30770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24466

East Asian (EAS) AF: 0.00 AC: 0 AN: 34780

South Asian (SAS) AF: 0.00 AC: 0 AN: 74636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1072064

Other (OTH) AF: 0.0000175 AC: 1 AN: 57202

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.55
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.082	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.90	T
PhyloP100		-0.81
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.077
Vest4		0.27
MutPred		0.29		Gain of ubiquitination at K55 (P = 0.0797)
MVP		0.040
ClinPred		0.18	T
GERP RS		-5.0
PromoterAI		0.0019	Neutral
Varity_R		0.30
gMVP		0.0074
Mutation Taster		=98/2	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: rs199854635; hg19: chr21-32090926;