17-8797619-C-A

Variant names:

• chr17-8797619-C-A
• rs192487452
• NM_152599.4:c.1502G>T

Variant summary

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

The NM_152599.4(MFSD6L):​c.1502G>T​(p.Gly501Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MFSD6L NM_152599.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.822
• Publications: 0 publications found

Genes affected

MFSD6L (HGNC:26656): (major facilitator superfamily domain containing 6 like) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD6L Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152599.4. 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
	MFSD6L	NM_152599.4	MANE Select	c.1502G>T	p.Gly501Val	missense	Exon 1 of 1	NP_689812.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD6L	ENST00000329805.6	TSL:6 MANE Select	c.1502G>T	p.Gly501Val	missense	Exon 1 of 1	ENSP00000330051.4	Q8IWD5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.14
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.82
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.26
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.25
MutPred		0.71		Loss of catalytic residue at G501 (P = 0.0651)
MVP		0.42
MPC		0.27
ClinPred		0.96	D
GERP RS		1.6
Varity_R		0.24
gMVP		0.46

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: rs192487452; hg19: chr17-8700937;