rs148914897

Variant names:

• chr22-50220708-A-G
• rs148914897
• NM_020461.4:c.3651T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-50220708-A-G
• chr22-50220708-A-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_020461.4(TUBGCP6):​c.3651T>C​(p.His1217His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,592,820 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: TUBGCP6 NM_020461.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.549
• Publications: 1 publications found

Genes affected

TUBGCP6 (HGNC:18127): (tubulin gamma complex component 6) The protein encoded by this gene is part of a large multisubunit complex required for microtubule nucleation at the centrosome. [provided by RefSeq, Jul 2008]

TUBGCP6 Gene-Disease associations (from GenCC):

• microcephaly and chorioretinopathy 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 22-50220708-A-G is Benign according to our data. Variant chr22-50220708-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 437166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.549 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00144 (195/135656) while in subpopulation AFR AF = 0.00501 (178/35534). AF 95% confidence interval is 0.00441. There are 0 homozygotes in GnomAd4. There are 97 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020461.4. 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
	TUBGCP6	NM_020461.4	MANE Select	c.3651T>C	p.His1217His	synonymous	Exon 16 of 25	NP_065194.3	Q96RT7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	ENST00000248846.10	TSL:1 MANE Select	c.3651T>C	p.His1217His	synonymous	Exon 16 of 25	ENSP00000248846.5	Q96RT7-1
	TUBGCP6	ENST00000439308.7	TSL:1	n.3651T>C		non_coding_transcript_exon	Exon 16 of 25	ENSP00000397387.2	E7EQL8
	TUBGCP6	ENST00000498611.5	TSL:1	n.3617+567T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 192 AN: 135560 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000461

Gnomad SAS AF: 0.000727

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000158

Gnomad OTH AF: 0.00106

GnomAD2 exomes AF: 0.000291 AC: 73 AN: 251084 AF XY: 0.000228

Gnomad AFR exome AF: 0.00376

Gnomad AMR exome AF: 0.0000872

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000105 AC: 153 AN: 1457164 Hom.: 1 Cov.: 39 AF XY: 0.0000841 AC XY: 61 AN XY: 725064

African (AFR) AF: 0.00348 AC: 116 AN: 33290

American (AMR) AF: 0.000114 AC: 5 AN: 43732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39424

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86152

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53144

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5748

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109630

Other (OTH) AF: 0.000316 AC: 19 AN: 60110

GnomAD4 genome AF: 0.00144 AC: 195 AN: 135656 Hom.: 0 Cov.: 32 AF XY: 0.00147 AC XY: 97 AN XY: 65870

African (AFR) AF: 0.00501 AC: 178 AN: 35534

American (AMR) AF: 0.000655 AC: 9 AN: 13740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3272

East Asian (EAS) AF: 0.000462 AC: 2 AN: 4328

South Asian (SAS) AF: 0.000727 AC: 3 AN: 4128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.0000158 AC: 1 AN: 63188

Other (OTH) AF: 0.00105 AC: 2 AN: 1902

Alfa AF: 0.000526 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.069
DANN	Benign	0.47
PhyloP100		-0.55
PromoterAI		0.046	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: rs148914897; hg19: chr22-50659137;