rs755996232

Variant names:

• chr7-100158248-C-G
• rs755996232
• NM_018275.5:c.252G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-100158248-C-G
• chr7-100158248-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_018275.5(TRAPPC14):​c.252G>C​(p.Ser84Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000308 in 1,487,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: TRAPPC14 NM_018275.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.824
• Publications: 0 publications found

Genes affected

TRAPPC14 (HGNC:25604): (trafficking protein particle complex subunit 14) Enables alpha-tubulin binding activity. Involved in cilium assembly and regulation of cell population proliferation. Located in several cellular components, including microtubule cytoskeleton; midbody; and plasma membrane. Part of TRAPPII protein complex. Implicated in primary autosomal recessive microcephaly. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC14 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-100158248-C-G is Benign according to our data. Variant chr7-100158248-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3056678.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.824 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018275.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC14	NM_018275.5	MANE Select	c.252G>C	p.Ser84Ser	synonymous	Exon 1 of 11	NP_060745.3
	TRAPPC14	NM_001303470.2		c.-396-310G>C		intron	N/A	NP_001290399.1	B3KNS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC14	ENST00000316937.8	TSL:1 MANE Select	c.252G>C	p.Ser84Ser	synonymous	Exon 1 of 11	ENSP00000324741.3	Q8WVR3-1
	TRAPPC14	ENST00000950372.1		c.252G>C	p.Ser84Ser	synonymous	Exon 1 of 11	ENSP00000620431.1
	TRAPPC14	ENST00000950373.1		c.252G>C	p.Ser84Ser	synonymous	Exon 1 of 11	ENSP00000620432.1

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000459 AC: 41 AN: 89274 AF XY: 0.000396

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000402

Gnomad ASJ exome AF: 0.00344

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.00186

GnomAD4 exome AF: 0.000298 AC: 398 AN: 1335332 Hom.: 1 Cov.: 32 AF XY: 0.000332 AC XY: 218 AN XY: 656818

African (AFR) AF: 0.000326 AC: 9 AN: 27580

American (AMR) AF: 0.000459 AC: 13 AN: 28336

Ashkenazi Jewish (ASJ) AF: 0.00525 AC: 119 AN: 22678

East Asian (EAS) AF: 0.00 AC: 0 AN: 31594

South Asian (SAS) AF: 0.000134 AC: 10 AN: 74358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32928

Middle Eastern (MID) AF: 0.00606 AC: 29 AN: 4784

European-Non Finnish (NFE) AF: 0.000160 AC: 169 AN: 1057630

Other (OTH) AF: 0.000884 AC: 49 AN: 55444

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30 AN XY: 74474

African (AFR) AF: 0.0000962 AC: 4 AN: 41576

American (AMR) AF: 0.000915 AC: 14 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68008

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.000557 Hom.: 0

Bravo AF: 0.000434

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TRAPPC14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		-0.82
PromoterAI		0.097	Neutral
Mutation Taster		=100/0	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: rs755996232; hg19: chr7-99755871; COSMIC: COSV57588042; COSMIC: COSV57588042;