chr2-113755494-C-T

Variant names:

• chr2-113755494-C-T
• rs375731808
• NM_025181.5:c.91G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025181.5(SLC35F5):​c.91G>A​(p.Gly31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: SLC35F5 NM_025181.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.684
• Publications: 2 publications found

Genes affected

SLC35F5 (HGNC:23617): (solute carrier family 35 member F5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC35F5 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02028203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35F5	NM_025181.5	c.91G>A	p.Gly31Ser	missense_variant	Exon 2 of 16	ENST00000245680.7	NP_079457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35F5	ENST00000245680.7	c.91G>A	p.Gly31Ser	missense_variant	Exon 2 of 16	1	NM_025181.5	ENSP00000245680.2
SLC35F5	ENST00000498768.1	n.269G>A		non_coding_transcript_exon_variant	Exon 2 of 7	1
SLC35F5	ENST00000409342.1	c.73G>A	p.Gly25Ser	missense_variant	Exon 2 of 7	2		ENSP00000386991.1
SLC35F5	ENST00000409106.5	n.73G>A		non_coding_transcript_exon_variant	Exon 2 of 17	2		ENSP00000386754.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000207 AC: 52 AN: 251244 AF XY: 0.000280

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000344 AC: 503 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.000389 AC XY: 283 AN XY: 727184

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000789 AC: 68 AN: 86236

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.000353 AC: 393 AN: 1111976

Other (OTH) AF: 0.000513 AC: 31 AN: 60392

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74410

African (AFR) AF: 0.0000482 AC: 2 AN: 41516

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000262 Hom.: 0

Bravo AF: 0.000166

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000181 AC: 22

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000534

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91G>A (p.G31S) alteration is located in exon 2 (coding exon 2) of the SLC35F5 gene. This alteration results from a G to A substitution at nucleotide position 91, causing the glycine (G) at amino acid position 31 to be replaced by a serine (S). 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
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0036	T;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.020	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
PhyloP100		0.68
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.29	N;.;N
REVEL	Benign	0.039
Sift	Benign	0.055	T;.;D
Sift4G	Benign	0.14	T;.;T
Polyphen		0.0020	B;.;B
Vest4		0.19
MVP		0.32
MPC		0.17
ClinPred		0.036	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.046
gMVP		0.24
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375731808; hg19: chr2-114513071;