Genetic Variant SPIC:p.Tyr116Tyr (chr12-101486372-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_152323.3(SPIC):c.348C>T(p.Tyr116Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,612,144 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 124 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 99 hom. )

Consequence

SPIC
NM_152323.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.659

Variant links:

Genes affected

SPIC (HGNC:29549): (Spi-C transcription factor) The protein encoded by this gene regulates the development of red pulp macrophages, which are necessary for iron homeostasis and the recycling of red blood cells. [provided by RefSeq, Aug 2016]

SPIC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 12-101486372-C-T is Benign according to our data. Variant chr12-101486372-C-T is described in ClinVar as [Benign]. Clinvar id is 784254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.659 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIC	NM_152323.3 link	c.348C>T	p.Tyr116Tyr	synonymous_variant	Exon 6 of 6	ENST00000551346.2	NP_689536.1	Q8N5J4
SPIC	XM_006719239.4 link	c.348C>T	p.Tyr116Tyr	synonymous_variant	Exon 6 of 6		XP_006719302.1	Q8N5J4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIC	ENST00000551346.2 link	c.348C>T	p.Tyr116Tyr	synonymous_variant	Exon 6 of 6	1	NM_152323.3	ENSP00000448580.1		Q8N5J4

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2972

AN:

152138

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0679

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

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:

0.00959

GnomAD3 exomes

AF:

0.00529

AC:

1326

AN:

250548

Hom.:

AF XY:

0.00382

AC XY:

518

AN XY:

135468

show subpopulations

Gnomad AFR exome

AF:

0.0702

Gnomad AMR exome

AF:

0.00403

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00214

AC:

3129

AN:

1459888

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1332

AN XY:

726086

show subpopulations

Gnomad4 AFR exome

AF:

0.0726

Gnomad4 AMR exome

AF:

0.00449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.00524

GnomAD4 genome

AF:

0.0198

AC:

3010

AN:

152256

Hom.:

124

Cov.:

AF XY:

0.0191

AC XY:

1422

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0686

Gnomad4 AMR

AF:

0.00752

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00949

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.0230

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.7

DANN

Benign

0.61

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

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