chr8-39610702-C-T

Variant names:

• chr8-39610702-C-T
• NM_014237.3:c.518C>T

Variant summary

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

The NM_014237.3(ADAM18):​c.518C>T​(p.Ser173Leu) 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. 15/22 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)
• Consequence: ADAM18 NM_014237.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.130
• Publications: 0 publications found

Genes affected

ADAM18 (HGNC:196): (ADAM metallopeptidase domain 18) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature sperm surface protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

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=0.11921987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014237.3. 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
	ADAM18	NM_014237.3	MANE Select	c.518C>T	p.Ser173Leu	missense	Exon 6 of 20	NP_055052.1	Q9Y3Q7-1
	ADAM18	NM_001320313.2		c.518C>T	p.Ser173Leu	missense	Exon 6 of 19	NP_001307242.1	Q9Y3Q7-2
	ADAM18	NM_001190956.2		c.518C>T	p.Ser173Leu	missense	Exon 6 of 6	NP_001177885.1	Q9Y3Q7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM18	ENST00000265707.10	TSL:1 MANE Select	c.518C>T	p.Ser173Leu	missense	Exon 6 of 20	ENSP00000265707.5	Q9Y3Q7-1
	ADAM18	ENST00000379866.5	TSL:1	c.518C>T	p.Ser173Leu	missense	Exon 6 of 19	ENSP00000369195.1	Q9Y3Q7-2
	ADAM18	ENST00000520772.5	TSL:1	c.518C>T	p.Ser173Leu	missense	Exon 6 of 6	ENSP00000429908.1	Q9Y3Q7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.079
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.043	N
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.13
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.044
Sift	Benign	0.038	D
Sift4G	Benign	0.34	T
Polyphen		0.043	B
Vest4		0.15
MutPred		0.45		Loss of disorder (P = 0.0441)
MVP		0.40
MPC		0.017
ClinPred		0.11	T
GERP RS		3.1
Varity_R		0.073
gMVP		0.31
Mutation Taster		=96/4	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

hg19: chr8-39468221;