7-892317-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_015949.3(GET4):​c.645C>T​(p.Val215Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,594,456 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00096 ( 22 hom. )

Consequence

GET4
NM_015949.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.483
Variant links:
Genes affected
GET4 (HGNC:21690): (guided entry of tail-anchored proteins factor 4) Enables chaperone binding activity. Involved in cytoplasmic sequestering of protein; maintenance of unfolded protein involved in ERAD pathway; and tail-anchored membrane protein insertion into ER membrane. Located in chromosome; cytosol; and nuclear lumen. Part of BAT3 complex. [provided by Alliance of Genome Resources, Apr 2022]
SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 7-892317-C-T is Benign according to our data. Variant chr7-892317-C-T is described in ClinVar as [Benign]. Clinvar id is 785870.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.483 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00185 (282/152340) while in subpopulation AMR AF= 0.0176 (270/15300). AF 95% confidence interval is 0.0159. There are 2 homozygotes in gnomad4. There are 172 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GET4NM_015949.3 linkc.645C>T p.Val215Val synonymous_variant Exon 6 of 9 ENST00000265857.8 NP_057033.2 Q7L5D6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GET4ENST00000265857.8 linkc.645C>T p.Val215Val synonymous_variant Exon 6 of 9 1 NM_015949.3 ENSP00000265857.3 Q7L5D6-1

Frequencies

GnomAD3 genomes
AF:
0.00186
AC:
283
AN:
152222
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0177
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:
0.0000294
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00456
AC:
1146
AN:
251190
Hom.:
20
AF XY:
0.00347
AC XY:
471
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.0324
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00294
GnomAD4 exome
AF:
0.000963
AC:
1389
AN:
1442116
Hom.:
22
Cov.:
31
AF XY:
0.000819
AC XY:
584
AN XY:
712636
show subpopulations
Gnomad4 AFR exome
AF:
0.000301
Gnomad4 AMR exome
AF:
0.0298
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000110
Gnomad4 OTH exome
AF:
0.000706
GnomAD4 genome
AF:
0.00185
AC:
282
AN:
152340
Hom.:
2
Cov.:
33
AF XY:
0.00231
AC XY:
172
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0176
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000523
Hom.:
0
Bravo
AF:
0.00322
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 15, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
5.7
DANN
Benign
0.90

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.

Other links and lift over

dbSNP: rs187709513; hg19: chr7-931954; API