Genetic Variant SERINC5:p.Leu419Leu (chr5-80113607-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_178276.7(SERINC5):c.1266G>A(p.Leu422Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 287,670 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

SERINC5
NM_178276.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.634

Variant links:

Genes affected

SERINC5 (HGNC:18825): (serine incorporator 5) Predicted to enable L-serine transmembrane transporter activity. Involved in defense response to virus; detection of virus; and innate immune response. Located in several cellular components, including centrosome; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SERINC5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 5-80113607-C-T is Benign according to our data. Variant chr5-80113607-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655566.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
SERINC5	NM_178276.7 link	c.1266G>A	p.Leu422Leu	synonymous_variant	Exon 12 of 13	NP_840060.1	Q86VE9-1
SERINC5	NM_001174071.3 link	c.1257G>A	p.Leu419Leu	synonymous_variant	Exon 12 of 13	NP_001167542.1	Q86VE9-2
SERINC5	NR_126060.2 link	n.1515G>A		non_coding_transcript_exon_variant	Exon 13 of 14
SERINC5	NR_126061.2 link	n.1569G>A		non_coding_transcript_exon_variant	Exon 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
SERINC5	ENST00000509193.5 link	c.1257G>A	p.Leu419Leu	synonymous_variant	Exon 12 of 13	1	ENSP00000426134.2	Q86VE9-2
SERINC5	ENST00000512972.6 link	n.*189G>A		non_coding_transcript_exon_variant	Exon 13 of 14	2	ENSP00000421665.2	Q86VE9-3
SERINC5	ENST00000632581.1 link	n.*18G>A		non_coding_transcript_exon_variant	Exon 13 of 14	2	ENSP00000488864.1	A0A0J9YYI4

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000235

AC:

AN:

55220

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

31438

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000304

Gnomad SAS exome

AF:

0.000114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000341

Gnomad OTH exome

AF:

0.00126

GnomAD4 exome

AF:

0.000362

AC:

AN:

135458

Hom.:

Cov.:

AF XY:

0.000400

AC XY:

AN XY:

82486

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000176

Gnomad4 ASJ exome

AF:

0.000220

Gnomad4 EAS exome

AF:

0.000561

Gnomad4 SAS exome

AF:

0.000231

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000459

Gnomad4 OTH exome

AF:

0.000667

GnomAD4 genome

AF:

0.000434

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000503

Hom.:

Bravo

AF:

0.000389

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SERINC5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.25

DANN

Benign

0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over