rs376966597

Variant names:

• chr11-65718251-C-A
• rs376966597
• NM_032193.4:c.*1532G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-65718251-C-A
• chr11-65718251-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032193.4(RNASEH2C):​c.*1532G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 83,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RNASEH2C NM_032193.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 0 publications found

Genes affected

RNASEH2C (HGNC:24116): (ribonuclease H2 subunit C) This gene encodes a ribonuclease H subunit that can cleave ribonucleotides from RNA:DNA duplexes. Mutations in this gene cause Aicardi-Goutieres syndrome-3, a disease that causes severe neurologic dysfunction. A pseudogene for this gene has been identified on chromosome Y, near the sex determining region Y (SRY) gene. [provided by RefSeq, Jul 2008]

KAT5 (HGNC:5275): (lysine acetyltransferase 5) The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

KAT5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

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 (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032193.4. 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
	RNASEH2C	NM_032193.4	MANE Select	c.*1532G>T		3_prime_UTR	Exon 4 of 4	NP_115569.2
	KAT5	NM_182710.3	MANE Select	c.1265-339C>A		intron	N/A	NP_874369.1	Q92993-3
	KAT5	NM_006388.4		c.1166-339C>A		intron	N/A	NP_006379.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2C	ENST00000308418.10	TSL:1 MANE Select	c.*1532G>T		3_prime_UTR	Exon 4 of 4	ENSP00000308193.5	Q8TDP1
	KAT5	ENST00000341318.9	TSL:1 MANE Select	c.1265-339C>A		intron	N/A	ENSP00000340330.4	Q92993-3
	KAT5	ENST00000377046.7	TSL:1	c.1166-339C>A		intron	N/A	ENSP00000366245.3	Q92993-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000120 AC: 1 AN: 83376 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 43496

⚠️ 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: 2936

American (AMR) AF: 0.00 AC: 0 AN: 4590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2492

East Asian (EAS) AF: 0.00 AC: 0 AN: 5586

South Asian (SAS) AF: 0.00 AC: 0 AN: 8042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 326

European-Non Finnish (NFE) AF: 0.0000195 AC: 1 AN: 51368

Other (OTH) AF: 0.00 AC: 0 AN: 4726

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.58
PhyloP100		0.22
PromoterAI		0.037	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs376966597; hg19: chr11-65485722;