chr12-53252834-C-T

Position:

• chr12-53252834-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000329548.5(MFSD5):​c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MFSD5 ENST00000329548.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49

Genes affected

MFSD5 (HGNC:28156): (major facilitator superfamily domain containing 5) Predicted to enable molybdate ion transmembrane transporter activity. Predicted to be involved in molybdate ion transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12253204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD5	NM_032889.5	c.-2C>T		5_prime_UTR_variant	2/2	ENST00000329548.5	NP_116278.3
MFSD5	NM_001170790.2	c.320C>T	p.Thr107Ile	missense_variant	2/2		NP_001164261.1
MFSD5	XM_005269197.2	c.320C>T	p.Thr107Ile	missense_variant	3/3		XP_005269254.1
MFSD5	XM_005269198.5	c.-2C>T		5_prime_UTR_variant	2/2		XP_005269255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD5	ENST00000329548.5	c.-2C>T		5_prime_UTR_variant	2/2	1	NM_032889.5	ENSP00000332624.5
MFSD5	ENST00000534842.1	c.320C>T	p.Thr107Ile	missense_variant	2/2	2		ENSP00000442688.1
MFSD5	ENST00000551660.2	c.320C>T	p.Thr107Ile	missense_variant	2/2	2		ENSP00000449354.2
MFSD5	ENST00000552097.1	n.52C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461344 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 726976

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.320C>T (p.T107I) alteration is located in exon 2 (coding exon 2) of the MFSD5 gene. This alteration results from a C to T substitution at nucleotide position 320, causing the threonine (T) at amino acid position 107 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.0	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.031	D;D
Vest4		0.12
MutPred		0.29		Loss of glycosylation at T107 (P = 0.0377);Loss of glycosylation at T107 (P = 0.0377);
MVP		0.19
MPC		0.28
ClinPred		0.34	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs1943431608; hg19: chr12-53646618; COSMIC: COSV100289226; COSMIC: COSV100289226;