13-36297700-T-C

Variant names:

• chr13-36297700-T-C
• ENST00000511166.1:c.-160A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198910.2(CCDC169-SOHLH2):​c.-160A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CCDC169-SOHLH2 NM_001198910.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.986
• Publications: 0 publications found

Genes affected

CCDC169-SOHLH2 (HGNC:38866): (CCDC169-SOHLH2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring C13orf38 (chromosome 13 open reading frame 38) and SOHLH2 (spermatogenesis and oogenesis specific basic helix-loop-helix 2) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

CCDC169 (HGNC:34361): (coiled-coil domain containing 169)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080114216).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198910.2. 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
	CCDC169	NM_001144981.3	MANE Select	c.20A>G	p.Tyr7Cys	missense	Exon 1 of 8	NP_001138453.1	A6NNP5-1
	CCDC169-SOHLH2	NM_001198910.2		c.-160A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	NP_001185839.1
	CCDC169	NM_001144984.3		c.-160A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001138456.1	A6NNP5-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC169-SOHLH2	ENST00000511166.1	TSL:2	c.-160A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000421868.1
	CCDC169	ENST00000239860.10	TSL:1	c.-160A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000239860.6	A6NNP5-6
	CCDC169	ENST00000379864.6	TSL:1	c.-207A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000369193.2	A6NNP5-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399022 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690038

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078962

Other (OTH) AF: 0.0000172 AC: 1 AN: 57996

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0332287), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.063
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.99
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.034
Sift	Benign	0.038	D
Sift4G	Uncertain	0.041	D
Polyphen		0.64	P
Vest4		0.12
MutPred		0.26		Gain of catalytic residue at V12 (P = 0.0055)
MVP		0.19
ClinPred		0.25	T
GERP RS		3.8
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.11
Mutation Taster		=99/1	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

hg19: chr13-36871837;