rs1456530912

Variant names:

• chr19-55358733-G-A
• rs1456530912
• NM_001145402.2:c.2135C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001145402.2(GARIN5B):​c.2135C>T​(p.Ser712Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,549,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: GARIN5B NM_001145402.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• Publications: 0 publications found

Genes affected

GARIN5B (HGNC:25278): (golgi associated RAB2 interactor family member 5B)

ENSG00000267706 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021095276).
• BP6: Variant 19-55358733-G-A is Benign according to our data. Variant chr19-55358733-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3098495.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARIN5B	NM_001145402.2	c.2135C>T	p.Ser712Leu	missense_variant	Exon 9 of 11	ENST00000424985.3	NP_001138874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARIN5B	ENST00000424985.3	c.2135C>T	p.Ser712Leu	missense_variant	Exon 9 of 11	5	NM_001145402.2	ENSP00000398617.1
ENSG00000267706	ENST00000591954.3	n.782C>T		non_coding_transcript_exon_variant	Exon 1 of 8	5		ENSP00000467419.1
GARIN5B	ENST00000585734.5	n.*1948C>T		non_coding_transcript_exon_variant	Exon 7 of 9	2		ENSP00000466418.1
GARIN5B	ENST00000585734.5	n.*1948C>T		3_prime_UTR_variant	Exon 7 of 9	2		ENSP00000466418.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00000654 AC: 1 AN: 152954 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000169

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000286 AC: 40 AN: 1397574 Hom.: 0 Cov.: 74 AF XY: 0.0000305 AC XY: 21 AN XY: 689082

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25090

East Asian (EAS) AF: 0.00 AC: 0 AN: 35698

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.0000334 AC: 36 AN: 1077900

Other (OTH) AF: 0.0000345 AC: 2 AN: 57918

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74382

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68036

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000602 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 08, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.033
DANN	Benign	0.84
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.12	N
PhyloP100		-1.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.0070
Sift	Benign	1.0	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.021
MVP		0.014
ClinPred		0.037	T
GERP RS		-5.8
Varity_R		0.021
gMVP		0.0075
Mutation Taster		=97/3	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

dbSNP: rs1456530912; hg19: chr19-55870101;