rs370467855

Variant names:

• chr12-101728682-TAGAG-T
• rs370467855
• NM_001177949.2:c.*241_*244delCTCT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001177949.2(SYCP3):​c.*241_*244delCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 519,402 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (15 hom.)
• Consequence: SYCP3 NM_001177949.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42
• Publications: 1 publications found

Genes affected

SYCP3 (HGNC:18130): (synaptonemal complex protein 3) This gene encodes an essential structural component of the synaptonemal complex. This complex is involved in synapsis, recombination and segregation of meiotic chromosomes. Mutations in this gene are associated with azoospermia in males and susceptibility to pregnancy loss in females. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2010]

CHPT1 (HGNC:17852): (choline phosphotransferase 1) Enables diacylglycerol cholinephosphotransferase activity. Involved in phosphatidylcholine biosynthetic process and platelet activating factor biosynthetic process. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-101728682-TAGAG-T is Benign according to our data. Variant chr12-101728682-TAGAG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 306758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00767 (2816/367078) while in subpopulation MID AF = 0.029 (45/1550). AF 95% confidence interval is 0.0223. There are 15 homozygotes in GnomAdExome4. There are 1457 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1005 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177949.2. 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
	SYCP3	NM_001177949.2	MANE Select	c.*241_*244delCTCT		3_prime_UTR	Exon 9 of 9	NP_001171420.1	Q8IZU3
	CHPT1	NM_020244.3	MANE Select	c.1177-215_1177-212delGAGA		intron	N/A	NP_064629.2	Q8WUD6-1
	SYCP3	NM_001177948.2		c.*241_*244delCTCT		3_prime_UTR	Exon 9 of 9	NP_001171419.1	Q8IZU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP3	ENST00000392924.2	TSL:1 MANE Select	c.*241_*244delCTCT		3_prime_UTR	Exon 9 of 9	ENSP00000376655.1	Q8IZU3
	SYCP3	ENST00000266743.6	TSL:1	c.*241_*244delCTCT		3_prime_UTR	Exon 9 of 9	ENSP00000266743.2	Q8IZU3
	SYCP3	ENST00000392927.7	TSL:1	c.*241_*244delCTCT		3_prime_UTR	Exon 9 of 9	ENSP00000376658.3	Q8IZU3

Frequencies

GnomAD3 genomes AF: 0.00661 AC: 1006 AN: 152206 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00895

Gnomad OTH AF: 0.00910

GnomAD4 exome AF: 0.00767 AC: 2816 AN: 367078 Hom.: 15 AF XY: 0.00754 AC XY: 1457 AN XY: 193232

African (AFR) AF: 0.00205 AC: 22 AN: 10728

American (AMR) AF: 0.0107 AC: 134 AN: 12560

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 294 AN: 11082

East Asian (EAS) AF: 0.00 AC: 0 AN: 24730

South Asian (SAS) AF: 0.00449 AC: 144 AN: 32098

European-Finnish (FIN) AF: 0.00266 AC: 57 AN: 21446

Middle Eastern (MID) AF: 0.0290 AC: 45 AN: 1550

European-Non Finnish (NFE) AF: 0.00825 AC: 1910 AN: 231640

Other (OTH) AF: 0.00989 AC: 210 AN: 21244

GnomAD4 genome AF: 0.00660 AC: 1005 AN: 152324 Hom.: 5 Cov.: 32 AF XY: 0.00648 AC XY: 483 AN XY: 74480

African (AFR) AF: 0.00183 AC: 76 AN: 41576

American (AMR) AF: 0.0101 AC: 155 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0234 AC: 81 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4828

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10628

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.00895 AC: 609 AN: 68014

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00637 Hom.: 2

Bravo AF: 0.00702

Asia WGS AF: 0.00203 AC: 7 AN: 3468

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Spermatogenic Failure (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
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: rs370467855; hg19: chr12-102122460; COSMIC: COSV57149713; COSMIC: COSV57149713;