21-30541779-C-T

Variant names:

• chr21-30541779-C-T
• rs1978780528
• NM_181612.3:c.55G>A

Variant summary

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

The NM_181612.3(KRTAP19-6):​c.55G>A​(p.Gly19Ser) 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. G19R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP19-6 NM_181612.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 0 publications found

Genes affected

KRTAP19-6 (HGNC:18941): (keratin associated protein 19-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000308278 (HGNC:):

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=0.060405374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181612.3. 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
	KRTAP19-6	NM_181612.3	MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 1	NP_853643.1	Q3LI70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP19-6	ENST00000334046.5	TSL:6 MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 1	ENSP00000375107.3	Q3LI70
	ENSG00000308278	ENST00000832954.1		n.124+10816C>T		intron	N/A
	ENSG00000308278	ENST00000832955.1		n.165+10816C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.4
DANN	Benign	0.40
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.55
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.032
Sift4G	Benign	0.10	T
Polyphen		0.051	B
Vest4		0.21
MutPred		0.22		Gain of glycosylation at G19 (P = 0.0012)
MVP		0.061
MPC		0.23
ClinPred		0.21	T
GERP RS		-5.9
PromoterAI		-0.0072	Neutral
Varity_R		0.42
gMVP		0.072
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: rs1978780528; hg19: chr21-31914098; COSMIC: COSV61844390; COSMIC: COSV61844390;