NM_152499.4:c.291C>T

Variant names:

• chr1-43992376-C-T
• rs74657675
• NM_152499.4:c.291C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_152499.4(CCDC24):​c.291C>T​(p.Ile97Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,614,182 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (29 hom.)
• Consequence: CCDC24 NM_152499.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.143
• Publications: 4 publications found

Genes affected

CCDC24 (HGNC:28688): (coiled-coil domain containing 24) Predicted to act upstream of or within blastocyst hatching. [provided by Alliance of Genome Resources, Apr 2022]

SLC6A9 (HGNC:11056): (solute carrier family 6 member 9) The amino acid glycine acts as an inhibitory neurotransmitter in the central nervous system. The protein encoded by this gene is one of two transporters that stop glycine signaling by removing it from the synaptic cleft. [provided by RefSeq, Jun 2016]

SLC6A9 Gene-Disease associations (from GenCC):

• atypical glycine encephalopathy

  Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen
• infantile glycine encephalopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP6: Variant 1-43992376-C-T is Benign according to our data. Variant chr1-43992376-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2638764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 29 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152499.4. 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
	CCDC24	NM_152499.4	MANE Select	c.291C>T	p.Ile97Ile	synonymous	Exon 3 of 9	NP_689712.1	Q8N4L8-1
	CCDC24	NM_001349128.1		c.291C>T	p.Ile97Ile	synonymous	Exon 2 of 8	NP_001336057.1
	CCDC24	NM_001349127.2		c.291C>T	p.Ile97Ile	synonymous	Exon 3 of 9	NP_001336056.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC24	ENST00000372318.8	TSL:1 MANE Select	c.291C>T	p.Ile97Ile	synonymous	Exon 3 of 9	ENSP00000361392.3	Q8N4L8-1
	CCDC24	ENST00000490563.5	TSL:1	n.611C>T		non_coding_transcript_exon	Exon 2 of 8
	CCDC24	ENST00000463846.5	TSL:1	n.126+372C>T		intron	N/A	ENSP00000476322.1	V9GYM6

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 594 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00650

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00403 AC: 1012 AN: 250908 AF XY: 0.00410

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00305

Gnomad NFE exome AF: 0.00610

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.00577 AC: 8433 AN: 1461836 Hom.: 29 Cov.: 33 AF XY: 0.00569 AC XY: 4135 AN XY: 727228

African (AFR) AF: 0.00128 AC: 43 AN: 33480

American (AMR) AF: 0.00157 AC: 70 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00520 AC: 136 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00335 AC: 289 AN: 86256

European-Finnish (FIN) AF: 0.00313 AC: 167 AN: 53408

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5766

European-Non Finnish (NFE) AF: 0.00665 AC: 7392 AN: 1111976

Other (OTH) AF: 0.00503 AC: 304 AN: 60394

GnomAD4 genome AF: 0.00390 AC: 594 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.00342 AC XY: 255 AN XY: 74490

African (AFR) AF: 0.00123 AC: 51 AN: 41574

American (AMR) AF: 0.00183 AC: 28 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4832

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00650 AC: 442 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00517 Hom.: 1

Bravo AF: 0.00362

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00534

EpiControl AF: 0.00640

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.28		Position offset: 11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs74657675; hg19: chr1-44458048;