chr6-109146800-G-A

Variant names:

• chr6-109146800-G-A
• rs922488370
• NM_001271852.3:c.203G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001271852.3(CEP57L1):​c.203G>A​(p.Arg68His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,597,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CEP57L1 NM_001271852.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53
• Publications: 1 publications found

Genes affected

CEP57L1 (HGNC:21561): (centrosomal protein 57 like 1) Enables identical protein binding activity. Predicted to be located in cytoplasm and microtubule. Predicted to be active in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08498958).
• BP6: Variant 6-109146800-G-A is Benign according to our data. Variant chr6-109146800-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2269634.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271852.3. 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
	CEP57L1	NM_001271852.3	MANE Select	c.203G>A	p.Arg68His	missense	Exon 3 of 11	NP_001258781.1	Q8IYX8-1
	CEP57L1	NM_001350654.2		c.203G>A	p.Arg68His	missense	Exon 3 of 11	NP_001337583.1
	CEP57L1	NM_001350655.2		c.203G>A	p.Arg68His	missense	Exon 4 of 12	NP_001337584.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP57L1	ENST00000517392.6	TSL:2 MANE Select	c.203G>A	p.Arg68His	missense	Exon 3 of 11	ENSP00000427844.1	Q8IYX8-1
	CEP57L1	ENST00000359793.7	TSL:1	c.203G>A	p.Arg68His	missense	Exon 3 of 11	ENSP00000352841.3	Q8IYX8-1
	CEP57L1	ENST00000368970.6	TSL:5	c.203G>A	p.Arg68His	missense	Exon 3 of 11	ENSP00000357966.2	E5RFY4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151780 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000426 AC: 1 AN: 234594 AF XY: 0.00000784

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000214 AC: 31 AN: 1445396 Hom.: 0 Cov.: 30 AF XY: 0.0000223 AC XY: 16 AN XY: 718756

African (AFR) AF: 0.0000311 AC: 1 AN: 32190

American (AMR) AF: 0.0000241 AC: 1 AN: 41562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25704

East Asian (EAS) AF: 0.0000520 AC: 2 AN: 38492

South Asian (SAS) AF: 0.0000361 AC: 3 AN: 83070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.0000199 AC: 22 AN: 1105722

Other (OTH) AF: 0.0000335 AC: 2 AN: 59752

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151780 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74100

African (AFR) AF: 0.00 AC: 0 AN: 41336

American (AMR) AF: 0.0000658 AC: 1 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	N
PhyloP100		1.5
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.088
Sift	Benign	0.15	T
Sift4G	Benign	0.19	T
Polyphen		0.70	P
Vest4		0.24
MVP		0.34
MPC		0.062
ClinPred		0.18	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.064
gMVP		0.31
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs922488370; hg19: chr6-109468003;