NM_173853.4:c.109G>C

Variant names:

• chr2-27442659-G-C
• rs1310514166
• NM_173853.4:c.109G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173853.4(KRTCAP3):​c.109G>C​(p.Ala37Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,431,356 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A37S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRTCAP3 NM_173853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26
• Publications: 0 publications found

Genes affected

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173853.4. 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
	KRTCAP3	NM_173853.4	MANE Select	c.109G>C	p.Ala37Pro	missense	Exon 2 of 7	NP_776252.2	Q53RY4-1
	KRTCAP3	NM_001168364.2		c.109G>C	p.Ala37Pro	missense	Exon 2 of 7	NP_001161836.1	Q53RY4-1
	KRTCAP3	NM_001321325.2		c.109G>C	p.Ala37Pro	missense	Exon 2 of 7	NP_001308254.1	Q53RY4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTCAP3	ENST00000288873.7	TSL:1 MANE Select	c.109G>C	p.Ala37Pro	missense	Exon 2 of 7	ENSP00000288873.3	Q53RY4-1
	KRTCAP3	ENST00000543753.5	TSL:5	c.109G>C	p.Ala37Pro	missense	Exon 2 of 7	ENSP00000442400.1	Q53RY4-1
	KRTCAP3	ENST00000872248.1		c.109G>C	p.Ala37Pro	missense	Exon 2 of 7	ENSP00000542307.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1431356 Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 2 AN XY: 709138

African (AFR) AF: 0.00 AC: 0 AN: 32686

American (AMR) AF: 0.00 AC: 0 AN: 41138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39358

South Asian (SAS) AF: 0.00 AC: 0 AN: 81744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1096830

Other (OTH) AF: 0.00 AC: 0 AN: 58838

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.3
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.81		Loss of helix (P = 0.0237)
MVP		0.78
MPC		0.69
ClinPred		0.98	D
GERP RS		4.1
PromoterAI		-0.0044	Neutral
Varity_R		0.89
gMVP		0.88
Mutation Taster		=37/63	disease causing

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: rs1310514166; hg19: chr2-27665526;