dbSNP rs2108389: GIPC3:c.*1402T>C (chr19-3591592-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001411144.1(GIPC3):c.2354T>C(p.Ile785Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,232,466 control chromosomes in the GnomAD database, including 191,709 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 30077 hom., cov: 31)

Exomes 𝑓: 0.54 ( 161632 hom. )

Consequence

GIPC3
NM_001411144.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.432

Variant links:

Genes affected

GIPC3 (HGNC:18183): (GIPC PDZ domain containing family member 3) The protein encoded by this gene belongs to the GIPC family. Studies in mice suggest that this gene is required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion in the ear. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2011]

GIPC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012926161).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIPC3	NM_133261.3 link	c.*1402T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000644452.3	NP_573568.1	Q8TF64
GIPC3	NM_001411144.1 link	c.2354T>C	p.Ile785Thr	missense_variant	Exon 6 of 6		NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3 link	c.*1402T>C		3_prime_UTR_variant	Exon 6 of 6		NM_133261.3	ENSP00000493901.2		Q8TF64
GIPC3	ENST00000644946.1 link	c.2354T>C	p.Ile785Thr	missense_variant	Exon 6 of 6			ENSP00000495068.1		A0A2R8Y651

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91802

AN:

151714

Hom.:

30033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.607

GnomAD4 exome

AF:

0.541

AC:

584530

AN:

1080634

Hom.:

161632

Cov.:

AF XY:

0.540

AC XY:

275531

AN XY:

510360

show subpopulations

Gnomad4 AFR exome

AF:

0.865

AC:

19878

AN:

22984

Gnomad4 AMR exome

AF:

0.448

AC:

3777

AN:

8428

Gnomad4 ASJ exome

AF:

0.551

AC:

7936

AN:

14402

Gnomad4 EAS exome

AF:

0.174

AC:

4607

AN:

26540

Gnomad4 SAS exome

AF:

0.395

AC:

7735

AN:

19606

Gnomad4 FIN exome

AF:

0.515

AC:

10989

AN:

21350

Gnomad4 NFE exome

AF:

0.548

AC:

504888

AN:

920692

Gnomad4 Remaining exome

AF:

0.527

AC:

23052

AN:

43714

Heterozygous variant carriers

15838

31677

47515

63354

79192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

16398

32796

49194

65592

81990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.605

AC:

91900

AN:

151832

Hom.:

30077

Cov.:

AF XY:

0.597

AC XY:

44285

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.847

AC:

0.846974

AN:

0.846974

Gnomad4 AMR

AF:

0.499

AC:

0.498884

AN:

0.498884

Gnomad4 ASJ

AF:

0.561

AC:

0.561166

AN:

0.561166

Gnomad4 EAS

AF:

0.164

AC:

0.163619

AN:

0.163619

Gnomad4 SAS

AF:

0.371

AC:

0.371452

AN:

0.371452

Gnomad4 FIN

AF:

0.511

AC:

0.511022

AN:

0.511022

Gnomad4 NFE

AF:

0.552

AC:

0.552053

AN:

0.552053

Gnomad4 OTH

AF:

0.604

AC:

0.604286

AN:

0.604286

Heterozygous variant carriers

1654

3308

4963

6617

8271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.572

Hom.:

72548

Bravo

AF:

0.611

TwinsUK

AF:

0.542

AC:

2008

ALSPAC

AF:

0.549

AC:

2116

Asia WGS

AF:

0.353

AC:

1230

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.95

DANN

Benign

0.51

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0013

GERP RS

-1.4

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over