rs200701146

Variant names:

• chr2-68980765-C-A
• rs200701146
• NM_019617.4:c.500C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-68980765-C-A
• chr2-68980765-C-T

Variant summary

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

The NM_019617.4(GKN1):​c.500C>A​(p.Thr167Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 6.9e-7 (0 hom.)
• Consequence: GKN1 NM_019617.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.65
• Publications: 4 publications found

Genes affected

GKN1 (HGNC:23217): (gastrokine 1) The protein encoded by this gene is found to be down-regulated in human gastric cancer tissue as compared to normal gastric mucosa. [provided by RefSeq, Jul 2008]

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=0.03483793).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019617.4. 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
	GKN1	NM_019617.4	MANE Select	c.500C>A	p.Thr167Lys	missense	Exon 6 of 6	NP_062563.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GKN1	ENST00000377938.4	TSL:1 MANE Select	c.500C>A	p.Thr167Lys	missense	Exon 6 of 6	ENSP00000367172.3	Q9NS71
	GKN1	ENST00000673932.3		c.542C>A	p.Thr181Lys	missense	Exon 6 of 6	ENSP00000501093.2	A0A8I5KHR1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445506 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 720476

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33162

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097180

Other (OTH) AF: 0.00 AC: 0 AN: 59884

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0010
DANN	Benign	0.18
DEOGEN2	Benign	0.019	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		-2.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.016
Sift	Benign	0.46	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.45		Gain of ubiquitination at T181 (P = 0.023)
MVP		0.22
MPC		0.21
ClinPred		0.040	T
GERP RS		-9.1
Varity_R		0.028
gMVP		0.45
Mutation Taster		=99/1	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: rs200701146; hg19: chr2-69207897;